Peripheral membrane protein
Encyclopedia
Peripheral membrane proteins are protein
s that adhere only temporarily to the biological membrane
with which they are associated. These molecules attach to integral membrane protein
s, or penetrate the peripheral regions of the lipid bilayer
. The regulatory protein subunits of many ion channel
s and transmembrane receptors, for example, may be defined as peripheral membrane proteins. In contrast to integral membrane proteins, peripheral membrane proteins tend to collect in the water-soluble component, or fraction, of all the proteins extracted during a protein purification
procedure. Proteins with GPI anchors are an exception to this rule and can have purification properties similar to those of integral membrane protein
s.
The reversible attachment of proteins to biological membranes has shown to regulate cell signaling
and many other important cellular events, through a variety of mechanisms.
For example, the close association between many enzyme
s and biological membranes may bring them into close proximity with their lipid substrate
(s).
Membrane binding may also promote rearrangement, dissociation, or conformational change
s within many protein structural domains, resulting in an activation of their biological activity.
Additionally, the positioning of many proteins are localized to either the inner or outer surfaces or leaflets of their resident membrane.
This facilitates the assembly of multi-protein complexes by increasing the probability of any appropriate protein–protein interactions.
Peripheral membrane proteins may interact with other proteins or directly with the lipid bilayer
. In the latter case, they are then known as amphitropic proteins.
Some proteins, such as G-proteins and certain protein kinase
s, interact with transmembrane proteins and the lipid bilayer simultaneously. Some polypeptide hormones, antimicrobial peptides
, and neurotoxins accumulate at the membrane surface prior to locating and interacting with their cell surface receptor targets, which may themselves be peripheral membrane proteins.
The phospholipid bilayer that forms the cell surface membrane consists of a hydrophobic inner core region sandwiched between two regions of hydrophilicity, one at the inner surface and one at the outer surface of the cell membrane (see lipid bilayer article for a more detailed structural description of the cell membrane). The inner and outer surfaces, or interfacial regions, of model phospholipid
bilayers have been shown to have a thickness of around 8 to 10 Å
, although this may be wider in biological membrane
s that include large amounts of ganglioside
s or lipopolysaccharide
s.
The hydrophobic inner core region of typical biological membranes may have a thickness of around 27 to 32 Å, as estimated by Small angle X-ray scattering (SAXS).
The boundary region between the hydrophobic inner core and the hydrophilic interfacial regions is very narrow, at around 3Å, (see lipid bilayer article for a description of its component chemical groups). Moving outwards away from the hydrophobic core region and into the interfacial hydrophilic region, the effective concentration of water rapidly changes across this boundary layer, from nearly zero to a concentration of around 2M.
The phosphate groups within phospholipid bilayers are fully hydrated or saturated with water and are situated around 5 Å outside the boundary of the hydrophobic core region (see Figures ).
Some water-soluble proteins associate with lipid bilayers irreversibly and can form transmembrane alpha-helical or beta-barrel channels. Such transformations occur in pore forming toxins
such as colicin
A, alpha-hemolysin, and others. They may also occur in cl-2-associated X protein|BcL-2 like protein , in some amphiphilic antimicrobial peptides
, and in certain annexin
s . These proteins are usually described as peripheral as one of their conformational states is water-soluble or only loosely associated with a membrane.
The association of a protein with a lipid bilayer
may involve significant changes within tertiary structure
of a protein. These may include the folding
of regions of protein structure that were previously unfolded or a re-arrangement in the folding or a refolding of the membrane-associated part of the proteins . It also may involve the formation or dissociation of protein quaternary structure
s or oligomeric complexes
, and specific binding of ion
s, ligands
, or regulatory lipids
.
Typical amphitropic proteins must interact strongly with the lipid bilayer in order to perform their biological functions. These include the enzymatic processing of lipids and other hydrophobic substances, membrane anchoring, and the binding and transfer of small nonpolar compounds between different cellular membranes. These proteins may be anchored to the bilayer as a result of hydrophobic interactions between the bilayer and exposed nonpolar residues at the surface of a protein, by specific non-covalent binding interactions with regulatory lipids , or through their attachment to covalently bound lipid anchors
.
It has been shown that the membrane binding affinities of many peripheral proteins depend on the specific lipid composition of the membrane with which they are associated.
s. Hydrophobic interactions have been shown to be important even for highly cationic peptides and proteins, such as the polybasic domain of the MARCKS protein
or histactophilin, when their natural hydrophobic anchors are present.
s are covalently attached to different fatty acid
acyl
chains on the cytoplasm
ic side of the cell membrane
via palmitoylation
, myristoylation
, or prenylation
. At the cell surface, on the opposite side of the cell membrane lipid anchored protein
s are covalently attached to the lipids glycosylphosphatidylinositol (GPI) and cholesterol
. Protein association with membranes through the use of acyl
ated residues is a reversible process
, as the acyl chain can be buried in a protein's hydrophobic binding pocket after dissociation from the membrane. This process occurs within the beta-subunits of G-proteins . Perhaps because of this additional need for structural flexibility, lipid anchors are usually bound to the highly flexible segments of proteins tertiary structure that are not well resolved by protein crystallographic studies.
Some cytosolic proteins are recruited to different cellular membranes by recognizing certain types of lipid found within a given membrane. Binding of a protein to a specific lipid occurs via specific membrane-targeting structural domains that occur within the protein and have specific binding pockets for the lipid head groups of the lipids to which they bind. This is a typical biochemical
protein–ligand
interaction, and is stabilized by the formation of intermolecular hydrogen bond
s, van der Waals interactions
, and hydrophobic interactions between the protein and lipid ligand
. Such complexes are also stabilized by the formation of ionic bridges between the aspartate or glutamate residues of the protein and lipid phosphates via interveening calcium
ions (Ca2+). Such ionic bridges can occur and are stable when ions (such as Ca2+) are already bound to a protein in solution, prior to lipid binding. The formation of ionic bridges is seen in the protein–lipid interaction between both protein C2 type domains
and annexin
s..
s, the outer leaflet of outer bacterial membranes and mitochondrial membranes. Therefore, electrostatic interactions play an important role in membrane targeting
of electron
carriers such as cytochrome c
, cationic toxins such as charybdotoxin
, and specific membrane-targeting domains such as some PH domains, C1 domain
s, and C2 domain
s.
Electrostatic interactions are strongly dependent on the ionic strength
of the solution. These interactions are relatively weak at the physiological ionic strength (0.14M NaCl): ~3 to 4 kcal/mol for small cationic proteins, such as cytochrome c
, charybdotoxin
or hisactophilin.
, chemical labeling, measurement of membrane binding affinities of protein mutants
, fluorescence
spectroscopy, solution or solid-state NMR spectroscopy
,
ATR FTIR spectroscopy
, X-ray or neutron diffraction, and computational methods.
Two distinct membrane-association modes of proteins have been identified. Typical water-soluble proteins have no exposed nonpolar residues or any other hydrophobic anchors. Therefore, they remain completely in aqueous solution and do not penetrate into the lipid bilayer, which would be energetically costly. Such proteins interact with bilayers only electrostatically, for example, ribonuclease
and poly-lysine interact with membranes in this mode. However, typical amphitropic proteins have various hydrophobic anchors that penetrate the interfacial region and reach the hydrocarbon interior of the membrane. Such proteins "deform" the lipid bilayer, decreasing the temperature of lipid fluid-gel transition. The binding is usually a strongly exothermic reaction. Association of amphiphilic α-helices with membranes occurs similarly. Intrinsically unstructured
or unfolded
peptides with nonpolar residues or lipid anchors can also penetrate the interfacial region of the membrane and reach the hydrocarbon core, especially when such peptides are cationic and interact with negatively charged membranes.
of different membrane components, such as lipid
s (phospholipases and cholesterol oxidases), cell wall
oligosaccharides (glycosyltransferase and transglycosidases), or proteins (signal peptidase and palmitoyl protein thioesterases). Lipases can also digest lipids that form micelle
s or nonpolar droplets in water.
Membrane-targeting domains associate specifically with head groups of their lipid ligands embedded into the membrane. These lipid ligands are present in different concentrations in distinct types of biological membranes (for example, PtdIns3P
can be found mostly in membranes of early endosome
s, PtdIns(3,5)P2
in late endosome
s, and PtdIns4P
in the Golgi
). Hence, each domain is targeted to a specific membrane.
ions (Ca2+) that form bridges between the acidic protein residues and phosphate groups of lipids, as in annexins or GLA domains.
s. They include cytochrome c
, cupredoxins
, high potential iron protein
, adrenodoxin reductase, some flavoprotein
s, and others.
s, toxins
, inhibitor
s, or antimicrobial peptides
interact specifically with transmembrane protein
complexes. They can also accumulate at the lipid bilayer surface, prior to binding their protein targets. Such polypeptide ligands are often positively charged and interact electrostatically
with anionic membranes.
Some water-soluble proteins and peptides can also form transmembrane channel
s. They usually undergo oligomer
ization, significant conformational change
s, and associate with membranes irreversibly. 3D structure of one such transmembrane channel, α-hemolysin
, has been determined. In other cases, the experimental structure represents a water-soluble conformation that interacts with the lipid bilayer peripherally, although some of the channel-forming peptides are rather hydrophobic and therefore were studied by NMR spectroscopy
in organic solvents or in the presence of micelles.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s that adhere only temporarily to the biological membrane
Biological membrane
A biological membrane or biomembrane is an enclosing or separatingmembrane that acts as a selective barrier, within or around a cell. It consists of a lipid bilayer with embedded proteins that may constitute close to 50% of membrane content...
with which they are associated. These molecules attach to integral membrane protein
Integral membrane protein
An integral membrane protein is a protein molecule that is permanently attached to the biological membrane. Proteins that cross the membrane are surrounded by "annular" lipids, which are defined as lipids that are in direct contact with a membrane protein...
s, or penetrate the peripheral regions of the lipid bilayer
Lipid bilayer
The lipid bilayer is a thin membrane made of two layers of lipid molecules. These membranes are flat sheets that form a continuous barrier around cells. The cell membrane of almost all living organisms and many viruses are made of a lipid bilayer, as are the membranes surrounding the cell nucleus...
. The regulatory protein subunits of many ion channel
Ion channel
Ion channels are pore-forming proteins that help establish and control the small voltage gradient across the plasma membrane of cells by allowing the flow of ions down their electrochemical gradient. They are present in the membranes that surround all biological cells...
s and transmembrane receptors, for example, may be defined as peripheral membrane proteins. In contrast to integral membrane proteins, peripheral membrane proteins tend to collect in the water-soluble component, or fraction, of all the proteins extracted during a protein purification
Protein purification
Protein purification is a series of processes intended to isolate a single type of protein from a complex mixture. Protein purification is vital for the characterization of the function, structure and interactions of the protein of interest. The starting material is usually a biological tissue or...
procedure. Proteins with GPI anchors are an exception to this rule and can have purification properties similar to those of integral membrane protein
Integral membrane protein
An integral membrane protein is a protein molecule that is permanently attached to the biological membrane. Proteins that cross the membrane are surrounded by "annular" lipids, which are defined as lipids that are in direct contact with a membrane protein...
s.
The reversible attachment of proteins to biological membranes has shown to regulate cell signaling
Cell signaling
Cell signaling is part of a complex system of communication that governs basic cellular activities and coordinates cell actions. The ability of cells to perceive and correctly respond to their microenvironment is the basis of development, tissue repair, and immunity as well as normal tissue...
and many other important cellular events, through a variety of mechanisms.
For example, the close association between many enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
s and biological membranes may bring them into close proximity with their lipid substrate
Substrate (biochemistry)
In biochemistry, a substrate is a molecule upon which an enzyme acts. Enzymes catalyze chemical reactions involving the substrate. In the case of a single substrate, the substrate binds with the enzyme active site, and an enzyme-substrate complex is formed. The substrate is transformed into one or...
(s).
Membrane binding may also promote rearrangement, dissociation, or conformational change
Conformational change
A macromolecule is usually flexible and dynamic. It can change its shape in response to changes in its environment or other factors; each possible shape is called a conformation, and a transition between them is called a conformational change...
s within many protein structural domains, resulting in an activation of their biological activity.
Additionally, the positioning of many proteins are localized to either the inner or outer surfaces or leaflets of their resident membrane.
This facilitates the assembly of multi-protein complexes by increasing the probability of any appropriate protein–protein interactions.
Binding of peripheral proteins to the lipid bilayer
Lipid bilayer
The lipid bilayer is a thin membrane made of two layers of lipid molecules. These membranes are flat sheets that form a continuous barrier around cells. The cell membrane of almost all living organisms and many viruses are made of a lipid bilayer, as are the membranes surrounding the cell nucleus...
. In the latter case, they are then known as amphitropic proteins.
Some proteins, such as G-proteins and certain protein kinase
Protein kinase
A protein kinase is a kinase enzyme that modifies other proteins by chemically adding phosphate groups to them . Phosphorylation usually results in a functional change of the target protein by changing enzyme activity, cellular location, or association with other proteins...
s, interact with transmembrane proteins and the lipid bilayer simultaneously. Some polypeptide hormones, antimicrobial peptides
Antimicrobial peptides
Antimicrobial peptides are an evolutionarily conserved component of the innate immune response and are found among all classes of life. Fundamental differences exist between prokaryotic and eukaryotic cells that may represent targets for antimicrobial peptides...
, and neurotoxins accumulate at the membrane surface prior to locating and interacting with their cell surface receptor targets, which may themselves be peripheral membrane proteins.
The phospholipid bilayer that forms the cell surface membrane consists of a hydrophobic inner core region sandwiched between two regions of hydrophilicity, one at the inner surface and one at the outer surface of the cell membrane (see lipid bilayer article for a more detailed structural description of the cell membrane). The inner and outer surfaces, or interfacial regions, of model phospholipid
Phospholipid
Phospholipids are a class of lipids that are a major component of all cell membranes as they can form lipid bilayers. Most phospholipids contain a diglyceride, a phosphate group, and a simple organic molecule such as choline; one exception to this rule is sphingomyelin, which is derived from...
bilayers have been shown to have a thickness of around 8 to 10 Å
Ångström
The angstrom or ångström, is a unit of length equal to 1/10,000,000,000 of a meter . Its symbol is the Swedish letter Å....
, although this may be wider in biological membrane
Biological membrane
A biological membrane or biomembrane is an enclosing or separatingmembrane that acts as a selective barrier, within or around a cell. It consists of a lipid bilayer with embedded proteins that may constitute close to 50% of membrane content...
s that include large amounts of ganglioside
Ganglioside
Ganglioside is a molecule composed of a glycosphingolipid with one or more sialic acids linked on the sugar chain. The 60+ known gangliosides differ mainly in the position and number of NANA residues.It is a component of the cell plasma membrane that modulates cell signal transduction events...
s or lipopolysaccharide
Lipopolysaccharide
Lipopolysaccharides , also known as lipoglycans, are large molecules consisting of a lipid and a polysaccharide joined by a covalent bond; they are found in the outer membrane of Gram-negative bacteria, act as endotoxins and elicit strong immune responses in animals.-Functions:LPS is the major...
s.
The hydrophobic inner core region of typical biological membranes may have a thickness of around 27 to 32 Å, as estimated by Small angle X-ray scattering (SAXS).
The boundary region between the hydrophobic inner core and the hydrophilic interfacial regions is very narrow, at around 3Å, (see lipid bilayer article for a description of its component chemical groups). Moving outwards away from the hydrophobic core region and into the interfacial hydrophilic region, the effective concentration of water rapidly changes across this boundary layer, from nearly zero to a concentration of around 2M.
The phosphate groups within phospholipid bilayers are fully hydrated or saturated with water and are situated around 5 Å outside the boundary of the hydrophobic core region (see Figures ).
Some water-soluble proteins associate with lipid bilayers irreversibly and can form transmembrane alpha-helical or beta-barrel channels. Such transformations occur in pore forming toxins
Pore forming toxins
Pore-forming toxins are protein toxins, typically , produced by bacteria, such as C.septicum and S.aureus. They are frequently cytotoxic , as they create unregulated pores in the membrane of targeted cells.-Types of PFTs:PFTs can be divided into the following subcategories:* Alpha-pore-forming...
such as colicin
Colicin
A colicin is a type of bacteriocin produced by and toxic to some strains of Escherichia coli. Colicins are released into the environment to reduce competition from other bacterial strains...
A, alpha-hemolysin, and others. They may also occur in cl-2-associated X protein|BcL-2 like protein , in some amphiphilic antimicrobial peptides
Antimicrobial peptides
Antimicrobial peptides are an evolutionarily conserved component of the innate immune response and are found among all classes of life. Fundamental differences exist between prokaryotic and eukaryotic cells that may represent targets for antimicrobial peptides...
, and in certain annexin
Annexin
Annexin is a common name for a group of cellular proteins. They are found in all kingdoms with the exception of the bacteria....
s . These proteins are usually described as peripheral as one of their conformational states is water-soluble or only loosely associated with a membrane.
Membrane binding mechanisms
Lipid bilayer
The lipid bilayer is a thin membrane made of two layers of lipid molecules. These membranes are flat sheets that form a continuous barrier around cells. The cell membrane of almost all living organisms and many viruses are made of a lipid bilayer, as are the membranes surrounding the cell nucleus...
may involve significant changes within tertiary structure
Tertiary structure
In biochemistry and molecular biology, the tertiary structure of a protein or any other macromolecule is its three-dimensional structure, as defined by the atomic coordinates.-Relationship to primary structure:...
of a protein. These may include the folding
Protein folding
Protein folding is the process by which a protein structure assumes its functional shape or conformation. It is the physical process by which a polypeptide folds into its characteristic and functional three-dimensional structure from random coil....
of regions of protein structure that were previously unfolded or a re-arrangement in the folding or a refolding of the membrane-associated part of the proteins . It also may involve the formation or dissociation of protein quaternary structure
Quaternary structure
In biochemistry, quaternary structure is the arrangement of multiple folded protein or coiling protein molecules in a multi-subunit complex.-Description and examples:...
s or oligomeric complexes
Oligomer
In chemistry, an oligomer is a molecule that consists of a few monomer units , in contrast to a polymer that, at least in principle, consists of an unlimited number of monomers. Dimers, trimers, and tetramers are oligomers. Many oils are oligomeric, such as liquid paraffin...
, and specific binding of ion
Ion
An ion is an atom or molecule in which the total number of electrons is not equal to the total number of protons, giving it a net positive or negative electrical charge. The name was given by physicist Michael Faraday for the substances that allow a current to pass between electrodes in a...
s, ligands
Ligand (biochemistry)
In biochemistry and pharmacology, a ligand is a substance that forms a complex with a biomolecule to serve a biological purpose. In a narrower sense, it is a signal triggering molecule, binding to a site on a target protein.The binding occurs by intermolecular forces, such as ionic bonds, hydrogen...
, or regulatory lipids
Phosphatidylinositol
Phosphatidylinositol is a negatively charged phospholipid and a minor component in the cytosolic side of eukaryotic cell membranes....
.
Typical amphitropic proteins must interact strongly with the lipid bilayer in order to perform their biological functions. These include the enzymatic processing of lipids and other hydrophobic substances, membrane anchoring, and the binding and transfer of small nonpolar compounds between different cellular membranes. These proteins may be anchored to the bilayer as a result of hydrophobic interactions between the bilayer and exposed nonpolar residues at the surface of a protein, by specific non-covalent binding interactions with regulatory lipids , or through their attachment to covalently bound lipid anchors
Lipid anchored protein
In lipid-anchored proteins, a covalently attached fatty acid such as palmitate or myristate serves to anchor them to either face of the cell membrane. Examples include G proteins and certain kinases. It is believed that the fatty acid chain inserts and assumes a place in the bilayer structure of...
.
It has been shown that the membrane binding affinities of many peripheral proteins depend on the specific lipid composition of the membrane with which they are associated.
Non-specific hydrophobic association
Amphitropic proteins associate with lipid bilayers via various hydrophobic anchor structures. Such as amphiphilic α-helixes, exposed nonpolar loops, post-translationally acylated or lipidated amino acid residues, or acyl chains of specifically bound regulatory lipids such as phosphatidylinositol phosphatePhosphatidylinositol
Phosphatidylinositol is a negatively charged phospholipid and a minor component in the cytosolic side of eukaryotic cell membranes....
s. Hydrophobic interactions have been shown to be important even for highly cationic peptides and proteins, such as the polybasic domain of the MARCKS protein
MARCKS protein
MARCKS proteins play important roles in cell shape, cell motility, secretion, transmembrane transport, and regulation of the cell cycle...
or histactophilin, when their natural hydrophobic anchors are present.
Covalently bound lipid anchors
Lipid anchored proteinLipid anchored protein
In lipid-anchored proteins, a covalently attached fatty acid such as palmitate or myristate serves to anchor them to either face of the cell membrane. Examples include G proteins and certain kinases. It is believed that the fatty acid chain inserts and assumes a place in the bilayer structure of...
s are covalently attached to different fatty acid
Fatty acid
In chemistry, especially biochemistry, a fatty acid is a carboxylic acid with a long unbranched aliphatic tail , which is either saturated or unsaturated. Most naturally occurring fatty acids have a chain of an even number of carbon atoms, from 4 to 28. Fatty acids are usually derived from...
acyl
Acyl
An acyl group is a functional group derived by the removal of one or more hydroxyl groups from an oxoacid, including inorganic acids.In organic chemistry, the acyl group is usually derived from a carboxylic acid . Therefore, it has the formula RCO-, where R represents an alkyl group that is...
chains on the cytoplasm
Cytoplasm
The cytoplasm is a small gel-like substance residing between the cell membrane holding all the cell's internal sub-structures , except for the nucleus. All the contents of the cells of prokaryote organisms are contained within the cytoplasm...
ic side of the cell membrane
Cell membrane
The cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...
via palmitoylation
Palmitoylation
S-Palmitoylation is the covalent attachment of fatty acids, such as palmitic acid, to cysteine residues of membrane proteins. The precise function of palmitoylation depends on the particular protein being considered. Palmitoylation enhances the hydrophobicity of proteins and contributes to their...
, myristoylation
Myristoylation
Myristoylation is an irreversible, co-translational protein modification found in animals, plants, fungi, protozoans and viruses. In this protein modification, a myristoyl group is covalently attached via an amide bond to the alpha-amino group of an N-terminal amino acid of a nascent polypeptide...
, or prenylation
Prenylation
Prenylation, or isoprenylation, or lipidation is the addition of hydrophobic molecules to a protein. It is usually assumed that prenyl groups facilitate attachment to cell membranes, similar to lipid anchor like the GPI anchor, though direct evidence is missing...
. At the cell surface, on the opposite side of the cell membrane lipid anchored protein
Lipid anchored protein
In lipid-anchored proteins, a covalently attached fatty acid such as palmitate or myristate serves to anchor them to either face of the cell membrane. Examples include G proteins and certain kinases. It is believed that the fatty acid chain inserts and assumes a place in the bilayer structure of...
s are covalently attached to the lipids glycosylphosphatidylinositol (GPI) and cholesterol
Cholesterol
Cholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...
. Protein association with membranes through the use of acyl
Acyl
An acyl group is a functional group derived by the removal of one or more hydroxyl groups from an oxoacid, including inorganic acids.In organic chemistry, the acyl group is usually derived from a carboxylic acid . Therefore, it has the formula RCO-, where R represents an alkyl group that is...
ated residues is a reversible process
Reversible process (thermodynamics)
In thermodynamics, a reversible process, or reversible cycle if the process is cyclic, is a process that can be "reversed" by means of infinitesimal changes in some property of the system without loss or dissipation of energy. Due to these infinitesimal changes, the system is in thermodynamic...
, as the acyl chain can be buried in a protein's hydrophobic binding pocket after dissociation from the membrane. This process occurs within the beta-subunits of G-proteins . Perhaps because of this additional need for structural flexibility, lipid anchors are usually bound to the highly flexible segments of proteins tertiary structure that are not well resolved by protein crystallographic studies.
Specific protein–lipid binding
Biochemistry
Biochemistry, sometimes called biological chemistry, is the study of chemical processes in living organisms, including, but not limited to, living matter. Biochemistry governs all living organisms and living processes...
protein–ligand
Ligand (biochemistry)
In biochemistry and pharmacology, a ligand is a substance that forms a complex with a biomolecule to serve a biological purpose. In a narrower sense, it is a signal triggering molecule, binding to a site on a target protein.The binding occurs by intermolecular forces, such as ionic bonds, hydrogen...
interaction, and is stabilized by the formation of intermolecular hydrogen bond
Hydrogen bond
A hydrogen bond is the attractive interaction of a hydrogen atom with an electronegative atom, such as nitrogen, oxygen or fluorine, that comes from another molecule or chemical group. The hydrogen must be covalently bonded to another electronegative atom to create the bond...
s, van der Waals interactions
Van der Waals force
In physical chemistry, the van der Waals force , named after Dutch scientist Johannes Diderik van der Waals, is the sum of the attractive or repulsive forces between molecules other than those due to covalent bonds or to the electrostatic interaction of ions with one another or with neutral...
, and hydrophobic interactions between the protein and lipid ligand
Ligand
In coordination chemistry, a ligand is an ion or molecule that binds to a central metal atom to form a coordination complex. The bonding between metal and ligand generally involves formal donation of one or more of the ligand's electron pairs. The nature of metal-ligand bonding can range from...
. Such complexes are also stabilized by the formation of ionic bridges between the aspartate or glutamate residues of the protein and lipid phosphates via interveening calcium
Calcium
Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...
ions (Ca2+). Such ionic bridges can occur and are stable when ions (such as Ca2+) are already bound to a protein in solution, prior to lipid binding. The formation of ionic bridges is seen in the protein–lipid interaction between both protein C2 type domains
C2 domain
A C2 domain is a protein structural domain involved in targeting proteins to cell membranes. It is a beta-sandwich composed of 8 β-strands that co-ordinates two or three calcium ions, which bind in a cavity formed by the first and final loops of the domain, on the membrane binding face.-Coupling...
and annexin
Annexin
Annexin is a common name for a group of cellular proteins. They are found in all kingdoms with the exception of the bacteria....
s..
Protein–lipid electrostatic interactions
Any positively charged protein will be attracted to a negatively charged membrane by nonspecific electrostatic interactions. However, not all peripheral peptides and proteins are cationic, and only certain sides of membrane are negatively charged. These include the cytoplasmic side of plasma membraneCell membrane
The cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...
s, the outer leaflet of outer bacterial membranes and mitochondrial membranes. Therefore, electrostatic interactions play an important role in membrane targeting
Protein targeting
Protein targeting or protein sorting is the mechanism by which a cell transports proteins to the appropriate positions in the cell or outside of it. Sorting targets can be the inner space of an organelle, any of several interior membranes, the cell's outer membrane, or its exterior via secretion...
of electron
Electron
The electron is a subatomic particle with a negative elementary electric charge. It has no known components or substructure; in other words, it is generally thought to be an elementary particle. An electron has a mass that is approximately 1/1836 that of the proton...
carriers such as cytochrome c
Cytochrome c
The Cytochrome complex, or cyt c is a small heme protein found loosely associated with the inner membrane of the mitochondrion. It belongs to the cytochrome c family of proteins. Cytochrome c is a highly soluble protein, unlike other cytochromes, with a solubility of about 100 g/L and is an...
, cationic toxins such as charybdotoxin
Charybdotoxin
Charybdotoxin is a 37 amino acid neurotoxin from the venom of the scorpion Leiurus quinquestriatus hebraeus that blocks calcium-activated potassium channels. This blockade causes hyperexcitability of the nervous system.-Chemical properties:...
, and specific membrane-targeting domains such as some PH domains, C1 domain
C1 domain
C1 domain binds an important secondary messenger diacylglycerol , as well as the analogous phorbol esters. Phorbol esters can directly stimulate protein kinase C, PKC...
s, and C2 domain
C2 domain
A C2 domain is a protein structural domain involved in targeting proteins to cell membranes. It is a beta-sandwich composed of 8 β-strands that co-ordinates two or three calcium ions, which bind in a cavity formed by the first and final loops of the domain, on the membrane binding face.-Coupling...
s.
Electrostatic interactions are strongly dependent on the ionic strength
Ionic strength
The ionic strength of a solution is a measure of the concentration of ions in that solution. Ionic compounds, when dissolved in water, dissociate into ions. The total electrolyte concentration in solution will affect important properties such as the dissociation or the solubility of different salts...
of the solution. These interactions are relatively weak at the physiological ionic strength (0.14M NaCl): ~3 to 4 kcal/mol for small cationic proteins, such as cytochrome c
Cytochrome c
The Cytochrome complex, or cyt c is a small heme protein found loosely associated with the inner membrane of the mitochondrion. It belongs to the cytochrome c family of proteins. Cytochrome c is a highly soluble protein, unlike other cytochromes, with a solubility of about 100 g/L and is an...
, charybdotoxin
Charybdotoxin
Charybdotoxin is a 37 amino acid neurotoxin from the venom of the scorpion Leiurus quinquestriatus hebraeus that blocks calcium-activated potassium channels. This blockade causes hyperexcitability of the nervous system.-Chemical properties:...
or hisactophilin.
Spatial position in membrane
Orientations and penetration depths of many amphitropic proteins and peptides in membranes are studied using site-directed spin labelingSite-directed spin labeling
Site-directed spin labeling is a technique for investigating protein local dynamics using electron spin resonance. The theory of SDSL is based on the specific reaction of spin labels with amino acids. A spin label's built-in protein structure can be detected by EPR spectroscopy...
, chemical labeling, measurement of membrane binding affinities of protein mutants
Mutagenesis
Mutagenesis is a process by which the genetic information of an organism is changed in a stable manner, resulting in a mutation. It may occur spontaneously in nature, or as a result of exposure to mutagens. It can also be achieved experimentally using laboratory procedures...
, fluorescence
Fluorescence
Fluorescence is the emission of light by a substance that has absorbed light or other electromagnetic radiation of a different wavelength. It is a form of luminescence. In most cases, emitted light has a longer wavelength, and therefore lower energy, than the absorbed radiation...
spectroscopy, solution or solid-state NMR spectroscopy
NMR spectroscopy
Nuclear magnetic resonance spectroscopy, most commonly known as NMR spectroscopy, is a research technique that exploits the magnetic properties of certain atomic nuclei to determine physical and chemical properties of atoms or the molecules in which they are contained...
,
ATR FTIR spectroscopy
Fourier transform spectroscopy
Fourier transform spectroscopy is a measurement technique whereby spectra are collected based on measurements of the coherence of a radiative source, using time-domain or space-domain measurements of the electromagnetic radiation or other type of radiation....
, X-ray or neutron diffraction, and computational methods.
Two distinct membrane-association modes of proteins have been identified. Typical water-soluble proteins have no exposed nonpolar residues or any other hydrophobic anchors. Therefore, they remain completely in aqueous solution and do not penetrate into the lipid bilayer, which would be energetically costly. Such proteins interact with bilayers only electrostatically, for example, ribonuclease
Ribonuclease
Ribonuclease is a type of nuclease that catalyzes the degradation of RNA into smaller components. Ribonucleases can be divided into endoribonucleases and exoribonucleases, and comprise several sub-classes within the EC 2.7 and 3.1 classes of enzymes.-Function:All organisms studied contain...
and poly-lysine interact with membranes in this mode. However, typical amphitropic proteins have various hydrophobic anchors that penetrate the interfacial region and reach the hydrocarbon interior of the membrane. Such proteins "deform" the lipid bilayer, decreasing the temperature of lipid fluid-gel transition. The binding is usually a strongly exothermic reaction. Association of amphiphilic α-helices with membranes occurs similarly. Intrinsically unstructured
Intrinsically unstructured proteins
Intrinsically unstructured proteins, often referred to as naturally unfolded proteins or disordered proteins, are proteins characterized by lack of stable tertiary structure when the protein exists as an isolated polypeptide chain under physiological conditions in vitro...
or unfolded
Denaturation (biochemistry)
Denaturation is a process in which proteins or nucleic acids lose their tertiary structure and secondary structure by application of some external stress or compound, such as a strong acid or base, a concentrated inorganic salt, an organic solvent , or heat...
peptides with nonpolar residues or lipid anchors can also penetrate the interfacial region of the membrane and reach the hydrocarbon core, especially when such peptides are cationic and interact with negatively charged membranes.
Enzymes
Peripheral enzymes participate in metabolismMetabolism
Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...
of different membrane components, such as lipid
Lipid
Lipids constitute a broad group of naturally occurring molecules that include fats, waxes, sterols, fat-soluble vitamins , monoglycerides, diglycerides, triglycerides, phospholipids, and others...
s (phospholipases and cholesterol oxidases), cell wall
Cell wall
The cell wall is the tough, usually flexible but sometimes fairly rigid layer that surrounds some types of cells. It is located outside the cell membrane and provides these cells with structural support and protection, and also acts as a filtering mechanism. A major function of the cell wall is to...
oligosaccharides (glycosyltransferase and transglycosidases), or proteins (signal peptidase and palmitoyl protein thioesterases). Lipases can also digest lipids that form micelle
Micelle
A micelle is an aggregate of surfactant molecules dispersed in a liquid colloid. A typical micelle in aqueous solution forms an aggregate with the hydrophilic "head" regions in contact with surrounding solvent, sequestering the hydrophobic single tail regions in the micelle centre. This phase is...
s or nonpolar droplets in water.
| Class | Function | Physiology | Structure |
|---|---|---|---|
| Alpha/beta hydrolase fold Alpha/beta hydrolase fold In molecular biology, the alpha/beta hydrolase fold is common to a number of hydrolytic enzymes of widely differing phylogenetic origin and catalytic function. The core of each enzyme is an alpha/beta-sheet , containing 8 strands connected byhelices... |
Catalyzes the hydrolysis Hydrolysis Hydrolysis is a chemical reaction during which molecules of water are split into hydrogen cations and hydroxide anions in the process of a chemical mechanism. It is the type of reaction that is used to break down certain polymers, especially those made by condensation polymerization... of chemical bonds. |
Includes bacteria Bacteria Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals... l, fungal, gastric and pancreatic lipase Lipase A lipase is an enzyme that catalyzes the formation or cleavage of fats . Lipases are a subclass of the esterases.Lipases perform essential roles in the digestion, transport and processing of dietary lipids in most, if not all, living organisms... s, palmitoyl protein thioesterase Thioesterase Thioesterases are enzymes which belong to the Esterase family. Esterases, in turn, are one type of the several hydrolases known.Thioesterases exhibit Esterase activity specifically at a thiol group.Thioesterases or thiolester hydrolases are identified as members of E.C.3.1.2.-Examples:Acetyl-coA... s, cutin Cutin Cutin is one of two waxy polymers that are the main components of the plant cuticle, which covers all aerial surfaces of plants. The other major cuticle polymer is cutan, which is much more readily preserved in the fossil record,... ase, and cholinesterase Cholinesterase In biochemistry, cholinesterase is a family of enzymes that catalyze the hydrolysis of the neurotransmitter acetylcholine into choline and acetic acid, a reaction necessary to allow a cholinergic neuron to return to its resting state after activation.-Types:... s |
http://opm.phar.umich.edu/families.php?superfamily=135 |
| Phospholipase A2 Phospholipase A2 Phospholipases A2 are enzymes that release fatty acids from the second carbon group of glycerol. This particular phospholipase specifically recognizes the sn-2 acyl bond of phospholipids and catalytically hydrolyzes the bond releasing arachidonic acid and lysophospholipids... (secretory and cytosolic) |
Hydrolysis of sn-2 fatty acid Fatty acid In chemistry, especially biochemistry, a fatty acid is a carboxylic acid with a long unbranched aliphatic tail , which is either saturated or unsaturated. Most naturally occurring fatty acids have a chain of an even number of carbon atoms, from 4 to 28. Fatty acids are usually derived from... bond of phospholipid Phospholipid Phospholipids are a class of lipids that are a major component of all cell membranes as they can form lipid bilayers. Most phospholipids contain a diglyceride, a phosphate group, and a simple organic molecule such as choline; one exception to this rule is sphingomyelin, which is derived from... s. |
Lipid digestion, membrane disruption, and lipid signaling Lipid signaling Lipid signaling, broadly defined, refers to any biological signaling event involving a lipid messenger that binds a protein target, such as a receptor, kinase or phosphatase, which in turn mediate the effects of these lipids on specific cellular responses... . |
http://opm.phar.umich.edu/families.php?superfamily=90 http://opm.phar.umich.edu/families.php?superfamily=134 |
| Phospholipase C Phospholipase C Phosphoinositide phospholipase C is a family of eukaryotic intracellular enzymes that play an important role in signal transduction processes. In general, this enzyme is denoted as Phospholipase C, although three other families of phospholipase C enzymes have been identified in bacteria and in... |
Hydrolyzes PIP2, a phosphatidylinositol Phosphatidylinositol Phosphatidylinositol is a negatively charged phospholipid and a minor component in the cytosolic side of eukaryotic cell membranes.... , into two second messagers, inositol triphosphate Inositol triphosphate Inositol trisphosphate or inositol 1,4,5-trisphosphate , together with diacylglycerol , is a secondary messenger molecule used in signal transduction and lipid signaling in biological cells. While DAG stays inside the membrane, IP3 is soluble and diffuses through the cell... and diacylglycerol Diglyceride A diglyceride, or a diacylglycerol , is a glyceride consisting of two fatty acid chains covalently bonded to a glycerol molecule through ester linkages.... . |
Lipid signaling Lipid signaling Lipid signaling, broadly defined, refers to any biological signaling event involving a lipid messenger that binds a protein target, such as a receptor, kinase or phosphatase, which in turn mediate the effects of these lipids on specific cellular responses... |
http://opm.phar.umich.edu/families.php?superfamily=126 |
| Cholesterol oxidases | Oxidizes and isomerizes cholesterol Cholesterol Cholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes... to cholest-4-en-3-one. |
Depletes cellular membranes of cholesterol, used in bacterial pathogenesis Pathogenesis The pathogenesis of a disease is the mechanism by which the disease is caused. The term can also be used to describe the origin and development of the disease and whether it is acute, chronic or recurrent... . |
http://opm.phar.umich.edu/families.php?superfamily=140 |
| Carotenoid oxygenase Carotenoid Oxygenase Carotenoid oxygenases are a family of enzymes involved in the cleavage of carotenoids to produce, for example, retinol, commonly known as vitamin A... |
Cleaves carotenoids. | Carotenoids function in both plants and animals as hormone Hormone A hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one... s (includes vitamin A Vitamin A Vitamin A is a vitamin that is needed by the retina of the eye in the form of a specific metabolite, the light-absorbing molecule retinal, that is necessary for both low-light and color vision... in humans), pigment Pigment A pigment is a material that changes the color of reflected or transmitted light as the result of wavelength-selective absorption. This physical process differs from fluorescence, phosphorescence, and other forms of luminescence, in which a material emits light.Many materials selectively absorb... s, flavor Flavor Flavor or flavour is the sensory impression of a food or other substance, and is determined mainly by the chemical senses of taste and smell. The "trigeminal senses", which detect chemical irritants in the mouth and throat as well as temperature and texture, are also very important to the overall... s, floral scents and defense compounds. |
http://opm.phar.umich.edu/families.php?superfamily=111 |
| Lipoxygenase Lipoxygenase Lipoxygenases are a family of iron-containing enzymes that catalyse the dioxygenation of polyunsaturated fatty acids in lipids containing a cis,cis-1,4- pentadiene structure. It catalyses the following reaction:... s |
Iron Iron Iron is a chemical element with the symbol Fe and atomic number 26. It is a metal in the first transition series. It is the most common element forming the planet Earth as a whole, forming much of Earth's outer and inner core. It is the fourth most common element in the Earth's crust... -containing enzymes that catalyze the dioxygenation Lipoxygenase Lipoxygenases are a family of iron-containing enzymes that catalyse the dioxygenation of polyunsaturated fatty acids in lipids containing a cis,cis-1,4- pentadiene structure. It catalyses the following reaction:... of polyunsaturated fatty acid Fatty acid In chemistry, especially biochemistry, a fatty acid is a carboxylic acid with a long unbranched aliphatic tail , which is either saturated or unsaturated. Most naturally occurring fatty acids have a chain of an even number of carbon atoms, from 4 to 28. Fatty acids are usually derived from... s. |
In animals lipoxygenases are involved in the synthesis of inflammatory Inflammation Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process... mediators known as leukotrienes. |
http://opm.phar.umich.edu/families.php?superfamily=87 |
| Alpha toxin Alpha toxin Alpha Toxin or alpha-toxin refers to several different protein toxins produced by bacteria. Alpha toxin may be:*Staphylococcus aureus alpha toxin, a membrane-disrupting toxin that creates pores causing hemolysis and tissue damage.... s |
Cleave phospholipid Phospholipid Phospholipids are a class of lipids that are a major component of all cell membranes as they can form lipid bilayers. Most phospholipids contain a diglyceride, a phosphate group, and a simple organic molecule such as choline; one exception to this rule is sphingomyelin, which is derived from... s in the cell membrane, similar to Phospholipase C. |
Bacterial pathogenesis, particularly by Clostridium perfringens Clostridium perfringens Clostridium perfringens is a Gram-positive, rod-shaped, anaerobic, spore-forming bacterium of the genus Clostridium. C. perfringens is ever present in nature and can be found as a normal component of decaying vegetation, marine sediment, the intestinal tract of humans and other vertebrates,... . |
http://opm.phar.umich.edu/families.php?superfamily=88 |
| Sphingomyelinase C | A phosphodiesterase Phosphodiesterase A phosphodiesterase is any enzyme that breaks a phosphodiester bond. Usually, people speaking of phosphodiesterase are referring to cyclic nucleotide phosphodiesterases, which have great clinical significance and are described below... , cleaves phosphodiester bonds. |
Processing of lipids such as sphingomyelin Sphingomyelin Sphingomyelin is a type of sphingolipid found in animal cell membranes, especially in the membranous myelin sheath that surrounds some nerve cell axons. It usually consists of phosphorylcholine and ceramide... . |
http://opm.phar.umich.edu/families.php?superfamily=148 |
| Glycosyltransferase Glycosyltransferase Glycosyltransferases are enzymes that act as a catalyst for the transfer of a monosaccharide unit from an activated nucleotide sugar to a glycosyl acceptor molecule, usually an alcohol.... s: MurG and Transglycosidases |
Catalyzes the transfer of sugar moieties from activated donor molecules to specific acceptor molecules, forming glycosidic bonds. | Biosynthesis of disaccharide Disaccharide A disaccharide or biose is the carbohydrate formed when two monosaccharides undergo a condensation reaction which involves the elimination of a small molecule, such as water, from the functional groups only. Like monosaccharides, disaccharides form an aqueous solution when dissolved in water... s, oligosaccharide Oligosaccharide An oligosaccharide is a saccharide polymer containing a small number of component sugars, also known as simple sugars... s and polysaccharide Polysaccharide Polysaccharides are long carbohydrate molecules, of repeated monomer units joined together by glycosidic bonds. They range in structure from linear to highly branched. Polysaccharides are often quite heterogeneous, containing slight modifications of the repeating unit. Depending on the structure,... s (glycoconjugates), MurG is involved in bacterial peptidoglycan Peptidoglycan Peptidoglycan, also known as murein, is a polymer consisting of sugars and amino acids that forms a mesh-like layer outside the plasma membrane of bacteria , forming the cell wall. The sugar component consists of alternating residues of β- linked N-acetylglucosamine and N-acetylmuramic acid... biosynthesis. |
http://opm.phar.umich.edu/families.php?superfamily=125 http://opm.phar.umich.edu/families.php?superfamily=136 |
| Ferrochelatase Ferrochelatase Ferrochelatase is an enzyme that catalyses the terminal step in the biosynthesis of heme, converting protoporphyrin IX into heme. It catalyses the reaction:A ferrochelatase enzyme consists of 497 amino acid residues with a m.w... |
Converts protoporphyrin IX Protoporphyrin IX Protoporphyrin IX, in the metabolism of porphyrin, is created by the enzyme protoporphyrinogen oxidase.-Heme b biosynthesis:In heme biosynthesis, the enzyme ferrochelatase converts it into heme b Protoporphyrin IX, in the metabolism of porphyrin, is created by the enzyme protoporphyrinogen... into heme Heme A heme or haem is a prosthetic group that consists of an iron atom contained in the center of a large heterocyclic organic ring called a porphyrin. Not all porphyrins contain iron, but a substantial fraction of porphyrin-containing metalloproteins have heme as their prosthetic group; these are... . |
Involved in porphyrin Porphyrin Porphyrins are a group of organic compounds, many naturally occurring. One of the best-known porphyrins is heme, the pigment in red blood cells; heme is a cofactor of the protein hemoglobin. Porphyrins are heterocyclic macrocycles composed of four modified pyrrole subunits interconnected at... metabolism, protoporphyrins are used to strengthen egg shells. |
http://opm.phar.umich.edu/families.php?superfamily=137 |
| Myotubularin-related protein family | Lipid phosphatase Phosphatase A phosphatase is an enzyme that removes a phosphate group from its substrate by hydrolysing phosphoric acid monoesters into a phosphate ion and a molecule with a free hydroxyl group . This action is directly opposite to that of phosphorylases and kinases, which attach phosphate groups to their... that dephosphorylates PtdIns3P Phosphatidylinositol 3-phosphate Phosphatidylinositol 3-phosphate is a phospholipid found in cell membranes that helps to recruit a range of proteins, many of which are involved in protein trafficking, to the membranes... and PtdIns(3,5)P2 Phosphatidylinositol (3,5)-bisphosphate Phosphatidylinositol -bisphosphate is a minor phospholipid component of cell membranes, yet important in distinguishing cell compartments... . |
Required for muscle Muscle Muscle is a contractile tissue of animals and is derived from the mesodermal layer of embryonic germ cells. Muscle cells contain contractile filaments that move past each other and change the size of the cell. They are classified as skeletal, cardiac, or smooth muscles. Their function is to... cell differentiation. |
http://opm.phar.umich.edu/families.php?superfamily=176 |
| Dihydroorotate dehydrogenases | Oxidation of dihydroorotate (DHO) to orotate. | Biosynthesis of pyrimidine Pyrimidine Pyrimidine is a heterocyclic aromatic organic compound similar to benzene and pyridine, containing two nitrogen atoms at positions 1 and 3 of the six-member ring... nucleotide Nucleotide Nucleotides are molecules that, when joined together, make up the structural units of RNA and DNA. In addition, nucleotides participate in cellular signaling , and are incorporated into important cofactors of enzymatic reactions... s in prokaryotic and eukaryotic cells. |
http://opm.phar.umich.edu/families.php?superfamily=59 |
| Glycolate oxidase | Catalyses the oxidation of α-hydroxy acids to the corresponding α-ketoacids. | In green plant Plant Plants are living organisms belonging to the kingdom Plantae. Precise definitions of the kingdom vary, but as the term is used here, plants include familiar organisms such as trees, flowers, herbs, bushes, grasses, vines, ferns, mosses, and green algae. The group is also called green plants or... s, the enzyme participates in photorespiration Photorespiration Photorespiration, or "'photo-respiration'", is a process in plant metabolism by which RuBP has oxygen added to it by the enzyme , instead of carbon dioxide during normal photosynthesis. This is the beginning step of the Calvin-Benson cycle... . In animals, the enzyme participates in production of oxalate Oxalate Oxalate , is the dianion with formula C2O42− also written 22−. Either name is often used for derivatives, such as disodium oxalate, 2C2O42−, or an ester of oxalic acid Oxalate (IUPAC: ethanedioate), is the dianion with formula C2O42− also written (COO)22−. Either... . |
http://opm.phar.umich.edu/families.php?superfamily=59 |
Membrane-targeting domains (“lipid clamps”)
Phosphatidylinositol 3-phosphate
Phosphatidylinositol 3-phosphate is a phospholipid found in cell membranes that helps to recruit a range of proteins, many of which are involved in protein trafficking, to the membranes...
can be found mostly in membranes of early endosome
Endosome
In biology, an endosome is a membrane-bound compartment inside eukaryotic cells. It is a compartment of the endocytic membrane transport pathway from the plasma membrane to the lysosome. Molecules internalized from the plasma membrane can follow this pathway all the way to lysosomes for...
s, PtdIns(3,5)P2
Phosphatidylinositol (3,5)-bisphosphate
Phosphatidylinositol -bisphosphate is a minor phospholipid component of cell membranes, yet important in distinguishing cell compartments...
in late endosome
Endosome
In biology, an endosome is a membrane-bound compartment inside eukaryotic cells. It is a compartment of the endocytic membrane transport pathway from the plasma membrane to the lysosome. Molecules internalized from the plasma membrane can follow this pathway all the way to lysosomes for...
s, and PtdIns4P
Phosphatidylinositol 4-phosphate
Phosphatidylinositol 4-phosphate is a precursor of Phosphatidylinositol -bisphosphate. PtdIns4P is prevalent in the membrane of the Golgi apparatus....
in the Golgi
Golgi apparatus
The Golgi apparatus is an organelle found in most eukaryotic cells. It was identified in 1898 by the Italian physician Camillo Golgi, after whom the Golgi apparatus is named....
). Hence, each domain is targeted to a specific membrane.
- C1 domainC1 domainC1 domain binds an important secondary messenger diacylglycerol , as well as the analogous phorbol esters. Phorbol esters can directly stimulate protein kinase C, PKC...
s http://opm.phar.umich.edu/families.php?superfamily=63 bind diacylglycerolDiglycerideA diglyceride, or a diacylglycerol , is a glyceride consisting of two fatty acid chains covalently bonded to a glycerol molecule through ester linkages....
and phorbol estersPhorbolPhorbol is a natural, plant-derived organic compound. It is a member of the tigliane family of diterpenes. It was first isolated in 1934 as the hydrolysis product of croton oil, which is derived from the seeds of Croton tiglium. Phorbol's structure was determined in 1967...
. - C2 domainC2 domainA C2 domain is a protein structural domain involved in targeting proteins to cell membranes. It is a beta-sandwich composed of 8 β-strands that co-ordinates two or three calcium ions, which bind in a cavity formed by the first and final loops of the domain, on the membrane binding face.-Coupling...
s http://opm.phar.umich.edu/families.php?superfamily=47 bind phosphatidylserinePhosphatidylserinePhosphatidylserine is a phospholipid component, usually kept on the inner-leaflet of cell membranes by an enzyme called flippase...
or phosphatidylcholinePhosphatidylcholinePhosphatidylcholines are a class of phospholipids that incorporate choline as a headgroup.They are a major component of biological membranes and can be easily obtained from a variety of readily available sources such as egg yolk or soy beans from which they are mechanically extracted or chemically... - Pleckstrin homology domainPleckstrin homology domainPleckstrin homology domain is a protein domain of approximately 120 amino acids that occurs in a wide range of proteins involved in intracellular signaling or as constituents of the cytoskeleton....
s http://opm.phar.umich.edu/families.php?superfamily=51, PX domainPX domainThe PX domain is a phosphoinositide-binding structural domain involved in targeting of proteins to cell membranes.This domain was first found in P40phox and p47phox domains of NADPH oxidase...
s http://opm.phar.umich.edu/families.php?superfamily=60, and Tubby domainsTubby proteinThe tubby protein is encoded by the TUB gene. It is an upstream cell signaling protein common to multicellular eukaryotes. The first tubby gene was identified in mice, and proteins that are homologous to tubby are known as "tubby-like proteins"...
http://opm.phar.umich.edu/families.php?superfamily=177 bind different phosphoinositidesPhosphatidylinositolPhosphatidylinositol is a negatively charged phospholipid and a minor component in the cytosolic side of eukaryotic cell membranes.... - FYVE domainFYVE domainFYVE zinc finger domain is named after the four cysteine-rich proteins: Fab 1 , YOTB, Vac 1 , and EEA1, in which it has been found....
s http://opm.phar.umich.edu/families.php?superfamily=62 are more specific for PtdIns3P. - ENTH domainENTH domainThe Epsin N-terminal homology domain is a structural domain that is found in proteins involved in endocytosis and cytoskeletal machinery.-Structure:...
s http://opm.phar.umich.edu/protein.php?pdbid=1h0a bind PtdIns(3,4)P2Phosphatidylinositol (3,4)-bisphosphatePhosphatidylinositol -bisphosphate is a minor phospholipid component of cell membranes, yet an important second messenger...
or PtdIns(4,5)P2Phosphatidylinositol (4,5)-bisphosphatePhosphatidylinositol 4,5-bisphosphate or PtdInsP2, also known simply as PIP2, is a minor phospholipid component of cell membranes...
. - ANTHAnthAnth was a 1994 Indian action film starring Sunil Shetty as Vijay, Somy Ali as Priya, Paresh Rawal as Dabala, and Deepak Shirke as Inspector Shirke. Mohan Joshi, Makrand Deshpande, Alok Nath and Vijendra Ghaat are also featured in the film. The film was directed by Sanjay Khanna, and produced by...
domain http://opm.phar.umich.edu/protein.php?pdbid=1hfa binds PtdIns(4,5)P2. - Proteins from ERM (ezrin/radixin/moesin) familyMerlin (protein)Merlin is a cytoskeletal protein. In humans, it is a tumor suppressor protein involved in Neurofibromatosis type II. Sequence data reveal its similarity to the ERM protein family....
http://opm.phar.umich.edu/protein.php?pdbid=1gc6 bind PtdIns(4,5)P2.
- Other phosphoinositidePhosphatidylinositolPhosphatidylinositol is a negatively charged phospholipid and a minor component in the cytosolic side of eukaryotic cell membranes....
-binding proteins include phosphotyrosine-binding domain http://opm.phar.umich.edu/protein.php?pdbid=1nu2 and certain PDZ domainPDZ domainThe PDZ domain is a common structural domain of 80-90 amino-acids found in the signaling proteins of bacteria, yeast, plants, viruses and animals...
s. They bind PtdIns(4,5)P2. - Discoidin domains of blood coagulationCoagulationCoagulation is a complex process by which blood forms clots. It is an important part of hemostasis, the cessation of blood loss from a damaged vessel, wherein a damaged blood vessel wall is covered by a platelet and fibrin-containing clot to stop bleeding and begin repair of the damaged vessel...
factors http://opm.phar.umich.edu/families.php?superfamily=48 - ENTH, VHS and ANTHAnthAnth was a 1994 Indian action film starring Sunil Shetty as Vijay, Somy Ali as Priya, Paresh Rawal as Dabala, and Deepak Shirke as Inspector Shirke. Mohan Joshi, Makrand Deshpande, Alok Nath and Vijendra Ghaat are also featured in the film. The film was directed by Sanjay Khanna, and produced by...
domains http://opm.phar.umich.edu/families.php?superfamily=39
Structural domains
Structural domains mediate attachment of other proteins to membranes. Their binding to membranes can be mediated by calciumCalcium
Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...
ions (Ca2+) that form bridges between the acidic protein residues and phosphate groups of lipids, as in annexins or GLA domains.
| Class | Function | Physiology | Structure |
|---|---|---|---|
| Annexin Annexin Annexin is a common name for a group of cellular proteins. They are found in all kingdoms with the exception of the bacteria.... s |
Calcium Calcium Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust... -dependent intracellular membrane/ phospholipid Phospholipid Phospholipids are a class of lipids that are a major component of all cell membranes as they can form lipid bilayers. Most phospholipids contain a diglyceride, a phosphate group, and a simple organic molecule such as choline; one exception to this rule is sphingomyelin, which is derived from... binding. |
Functions include vesicle Vesicle (biology) A vesicle is a bubble of liquid within another liquid, a supramolecular assembly made up of many different molecules. More technically, a vesicle is a small membrane-enclosed sack that can store or transport substances. Vesicles can form naturally because of the properties of lipid membranes , or... trafficking, membrane fusion and ion channel Ion channel Ion channels are pore-forming proteins that help establish and control the small voltage gradient across the plasma membrane of cells by allowing the flow of ions down their electrochemical gradient. They are present in the membranes that surround all biological cells... formation. |
http://opm.phar.umich.edu/families.php?superfamily=43 |
| Synapsin I Synapsin The synapsins are a family of proteins that have long been implicated in the regulation of neurotransmitter release at synapses. Specifically, they are thought to be involved in regulating the number of synaptic vesicles available for release via exocytosis at any one time.Current studies suggest... |
Coats synaptic vesicle Synaptic vesicle In a neuron, synaptic vesicles store various neurotransmitters that are released at the synapse. The release is regulated by a voltage-dependent calcium channel. Vesicles are essential for propagating nerve impulses between neurons and are constantly recreated by the cell... s and binds to several cytoskeletal elements. |
Functions in the regulation of neurotransmitter Neurotransmitter Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to... release. |
http://opm.phar.umich.edu/families.php?superfamily=131 |
| Synuclein Synuclein Synucleins are a family of soluble proteins common to vertebrates, primarily expressed in neural tissue and in certain tumors.- Family members :The synuclein family includes three known proteins: alpha-synuclein, beta-synuclein, and gamma-synuclein... |
Unknown cellular function. | Thought to play a role in regulating the stability and/or turnover of the plasma membrane. Associated with both Parkinson's disease Parkinson's disease Parkinson's disease is a degenerative disorder of the central nervous system... and Alzheimer's disease Alzheimer's disease Alzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death... . |
http://opm.phar.umich.edu/families.php?superfamily=159 |
| GLA-domains of the coagulation system Coagulation Coagulation is a complex process by which blood forms clots. It is an important part of hemostasis, the cessation of blood loss from a damaged vessel, wherein a damaged blood vessel wall is covered by a platelet and fibrin-containing clot to stop bleeding and begin repair of the damaged vessel... |
Gamma-carboxyglutamate (GLA) domains are responsible for the high-affinity binding of calcium ions. | Involved in function of clotting factors in the blood coagulation cascade. | http://opm.phar.umich.edu/families.php?superfamily=97 |
| Spectrin Spectrin Spectrin is a cytoskeletal protein that lines the intracellular side of the plasma membrane of many cell types in pentagonal or hexagonal arrangements, forming a scaffolding and playing an important role in maintenance of plasma membrane integrity and cytoskeletal structure... and α-actinin Actinin Actinin is a microfilament protein. α-Actinin is necessary for the attachment of actin filaments to the Z-lines in skeletal muscle cells, and to the dense bodies in smooth muscle cells... -2 |
Found in several cytoskeletal and microfilament Microfilament Microfilaments are the thinnest filaments of the cytoskeleton, a structure found in the cytoplasm of all eukaryotic cells. These linear polymers of actin subunits are flexible and relatively strong, resisting buckling by multi-piconewton compressive forces and filament fracture by nanonewton... proteins. |
Maintenance of plasma membrane integrity and cytoskeletal structure. | http://opm.phar.umich.edu/families.php?superfamily=79 |
Transporters of small hydrophobic molecules
These peripheral proteins function as carriers of non-polar compounds between different types of cell membranes or between membranes and cytosolic protein complexes. The transported substances are phosphatidylinositol, tocopherol, gangliosides, glycolipids, sterol derivatives, retinol, or fatty acids.- Glycolipid transfer proteinGlycolipid transfer proteinGlycolipid transfer protein is a cytosolic protein that catalyses the transfer of glycolipids between different intracellular membranes. This protein transport primarily different glycosphingolipids and glyceroglycolipids between intracellular membranes, but not phospholipids. It might be also...
s http://opm.phar.umich.edu/families.php?superfamily=92 - LipocalinLipocalinThe lipocalins are a family of proteins which transport small hydrophobic molecules such as steroids, bilins, retinoids, and lipids. They share limited regions of sequence homology and a common tertiary structure architecture...
s including retinol binding proteinRetinol binding proteinRetinol-binding proteins are a family of proteins with diverse functions. They are carrier proteins that bind retinol.Assessment of retinol-binding protein is used to determine visceral protein mass in nutritional studies related to health.-Genes:...
s and fatty acidFatty acidIn chemistry, especially biochemistry, a fatty acid is a carboxylic acid with a long unbranched aliphatic tail , which is either saturated or unsaturated. Most naturally occurring fatty acids have a chain of an even number of carbon atoms, from 4 to 28. Fatty acids are usually derived from...
-binding proteins http://opm.phar.umich.edu/families.php?superfamily=52 - Polyisoprenoid-binding protein http://opm.phar.umich.edu/families.php?superfamily=109
- Ganglioside GM2 activator proteins http://opm.phar.umich.edu/families.php?superfamily=114
- CRAL-TRIO domainCRAL-TRIO domainCRAL-TRIO domain is a protein structural domain that binds small lipophilic molecules. This domain is named after cellular retinaldehyde-binding protein and TRIO guanine exchange factor....
(α-TocopherolTocopherolTocopherols are a class of chemical compounds of which many have vitamin E activity. It is a series of organic compounds consisting of various methylated phenols...
and phosphatidylinositolPhosphatidylinositolPhosphatidylinositol is a negatively charged phospholipid and a minor component in the cytosolic side of eukaryotic cell membranes....
sec14p transfer proteins) http://opm.phar.umich.edu/families.php?superfamily=129 - Sterol carrier proteinSterol carrier proteinSterol carrier proteins is a family of proteins that transfer steroids and probably also phospholipids and gangliosides between cellular membranes....
s http://opm.phar.umich.edu/families.php?superfamily=144 - Phosphatidylinositol transfer proteins and STAR domainsSteroidogenic acute regulatory proteinThe steroidogenic acute regulatory protein, commonly referred to as StAR , is a transport protein that regulates cholesterol transfer within the mitochondria, which is the rate-limiting step in the production of steroid hormones...
http://opm.phar.umich.edu/families.php?superfamily=147 - Oxysterol-binding protein http://opm.phar.umich.edu/families.php?superfamily=173
Electron carriers
These proteins are involved in electron transport chainElectron transport chain
An electron transport chain couples electron transfer between an electron donor and an electron acceptor with the transfer of H+ ions across a membrane. The resulting electrochemical proton gradient is used to generate chemical energy in the form of adenosine triphosphate...
s. They include cytochrome c
Cytochrome c
The Cytochrome complex, or cyt c is a small heme protein found loosely associated with the inner membrane of the mitochondrion. It belongs to the cytochrome c family of proteins. Cytochrome c is a highly soluble protein, unlike other cytochromes, with a solubility of about 100 g/L and is an...
, cupredoxins
Copper proteins
Copper proteins are proteins that contain one or more copper ions as prosthetic groups. The metal centres in the copper proteins can be classified into several types:...
, high potential iron protein
Iron-sulfur protein
Iron-sulfur proteins are proteins characterized by the presence of iron-sulfur clusters containing sulfide-linked di-, tri-, and tetrairon centers in variable oxidation states...
, adrenodoxin reductase, some flavoprotein
Flavoprotein
Flavoproteins are proteins that contain a nucleic acid derivative of riboflavin: the flavin adenine dinucleotide or flavin mononucleotide ....
s, and others.
Polypeptide hormones, toxins, and antimicrobial peptides
Many hormoneHormone
A hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...
s, toxins
Neurotoxin
A neurotoxin is a toxin that acts specifically on nerve cells , usually by interacting with membrane proteins such as ion channels. Some sources are more general, and define the effect of neurotoxins as occurring at nerve tissue...
, inhibitor
Enzyme inhibitor
An enzyme inhibitor is a molecule that binds to enzymes and decreases their activity. Since blocking an enzyme's activity can kill a pathogen or correct a metabolic imbalance, many drugs are enzyme inhibitors. They are also used as herbicides and pesticides...
s, or antimicrobial peptides
Antimicrobial peptides
Antimicrobial peptides are an evolutionarily conserved component of the innate immune response and are found among all classes of life. Fundamental differences exist between prokaryotic and eukaryotic cells that may represent targets for antimicrobial peptides...
interact specifically with transmembrane protein
Transmembrane protein
A transmembrane protein is a protein that goes from one side of a membrane through to the other side of the membrane. Many TPs function as gateways or "loading docks" to deny or permit the transport of specific substances across the biological membrane, to get into the cell, or out of the cell as...
complexes. They can also accumulate at the lipid bilayer surface, prior to binding their protein targets. Such polypeptide ligands are often positively charged and interact electrostatically
Ionic bond
An ionic bond is a type of chemical bond formed through an electrostatic attraction between two oppositely charged ions. Ionic bonds are formed between a cation, which is usually a metal, and an anion, which is usually a nonmetal. Pure ionic bonding cannot exist: all ionic compounds have some...
with anionic membranes.
Some water-soluble proteins and peptides can also form transmembrane channel
Ion channel
Ion channels are pore-forming proteins that help establish and control the small voltage gradient across the plasma membrane of cells by allowing the flow of ions down their electrochemical gradient. They are present in the membranes that surround all biological cells...
s. They usually undergo oligomer
Oligomer
In chemistry, an oligomer is a molecule that consists of a few monomer units , in contrast to a polymer that, at least in principle, consists of an unlimited number of monomers. Dimers, trimers, and tetramers are oligomers. Many oils are oligomeric, such as liquid paraffin...
ization, significant conformational change
Conformational change
A macromolecule is usually flexible and dynamic. It can change its shape in response to changes in its environment or other factors; each possible shape is called a conformation, and a transition between them is called a conformational change...
s, and associate with membranes irreversibly. 3D structure of one such transmembrane channel, α-hemolysin
Hemolysis (microbiology)
Hemolysis is the breakdown of red blood cells. The ability of bacterial colonies to induce hemolysis when grown on blood agar is used to classify certain microorganisms. This is particularly useful in classifying streptococcal species...
, has been determined. In other cases, the experimental structure represents a water-soluble conformation that interacts with the lipid bilayer peripherally, although some of the channel-forming peptides are rather hydrophobic and therefore were studied by NMR spectroscopy
NMR spectroscopy
Nuclear magnetic resonance spectroscopy, most commonly known as NMR spectroscopy, is a research technique that exploits the magnetic properties of certain atomic nuclei to determine physical and chemical properties of atoms or the molecules in which they are contained...
in organic solvents or in the presence of micelles.
| Class | Proteins | Physiology |
|---|---|---|
| Venom Venom Venom is the general term referring to any variety of toxins used by certain types of animals that inject it into their victims by the means of a bite or a sting... toxin Toxin A toxin is a poisonous substance produced within living cells or organisms; man-made substances created by artificial processes are thus excluded... s |
|
Well known types of biotoxins include neurotoxins, cytotoxins, hemotoxin Hemotoxin Hemotoxins, haemotoxins or hematotoxins are toxins that destroy red blood cells , disrupt blood clotting, and/or cause organ degeneration and generalized tissue damage. The term hemotoxin is to some degree a misnomer since toxins that damage the blood also damage other tissues... s and necrotoxins. Biotoxins have two primary functions: predation (snake Snake Snakes are elongate, legless, carnivorous reptiles of the suborder Serpentes that can be distinguished from legless lizards by their lack of eyelids and external ears. Like all squamates, snakes are ectothermic, amniote vertebrates covered in overlapping scales... , scorpion Scorpion Scorpions are predatory arthropod animals of the order Scorpiones within the class Arachnida. They have eight legs and are easily recognized by the pair of grasping claws and the narrow, segmented tail, often carried in a characteristic forward curve over the back, ending with a venomous stinger... and cone snail Cone snail Conidae is a taxonomic family of minute to quite large sea snails, marine gastropod molluscs in the superfamily Conoidea.The snails within this family are sophisticated predatory animals... toxins) and defense (honeybee and ant Ant Ants are social insects of the family Formicidae and, along with the related wasps and bees, belong to the order Hymenoptera. Ants evolved from wasp-like ancestors in the mid-Cretaceous period between 110 and 130 million years ago and diversified after the rise of flowering plants. More than... toxins). |
| Sea anemone Sea anemone Sea anemones are a group of water-dwelling, predatory animals of the order Actiniaria; they are named after the anemone, a terrestrial flower. Sea anemones are classified in the phylum Cnidaria, class Anthozoa, subclass Zoantharia. Anthozoa often have large polyps that allow for digestion of larger... toxins |
Neurotoxin A neurotoxin is a toxin that acts specifically on nerve cells , usually by interacting with membrane proteins such as ion channels. Some sources are more general, and define the effect of neurotoxins as occurring at nerve tissue... http://opm.phar.umich.edu/families.php?superfamily=122 Cytolysin Cytolysin refers to the substance or antibody elaborated by microorganisms, plants or animals that is specifically toxic to individual cells, in many cases causing their dissolution through lysis. Cytolysins that have a specific action for certain cells are named accordingly... s http://opm.phar.umich.edu/families.php?superfamily=103 |
Inhibition of sodium and potassium channel Potassium channel In the field of cell biology, potassium channels are the most widely distributed type of ion channel and are found in virtually all living organisms. They form potassium-selective pores that span cell membranes... s and membrane pore formation Pore forming toxins Pore-forming toxins are protein toxins, typically , produced by bacteria, such as C.septicum and S.aureus. They are frequently cytotoxic , as they create unregulated pores in the membrane of targeted cells.-Types of PFTs:PFTs can be divided into the following subcategories:* Alpha-pore-forming... are the primary actions of over 40 known Sea anemone peptide toxins. Sea anemone are carnivorous animals and use toxins in predation Predation In ecology, predation describes a biological interaction where a predator feeds on its prey . Predators may or may not kill their prey prior to feeding on them, but the act of predation always results in the death of its prey and the eventual absorption of the prey's tissue through consumption... and defense; anemone toxin is of similar toxicity Toxicity Toxicity is the degree to which a substance can damage a living or non-living organisms. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a substructure of the organism, such as a cell or an organ , such as the liver... as the most toxic organophosphate Organophosphate An organophosphate is the general name for esters of phosphoric acid. Phosphates are probably the most pervasive organophosphorus compounds. Many of the most important biochemicals are organophosphates, including DNA and RNA as well as many cofactors that are essential for life... chemical warfare Chemical warfare Chemical warfare involves using the toxic properties of chemical substances as weapons. This type of warfare is distinct from Nuclear warfare and Biological warfare, which together make up NBC, the military acronym for Nuclear, Biological, and Chemical... agents. |
| Bacterial toxins |
Clostridium perfringens Clostridium perfringens is a Gram-positive, rod-shaped, anaerobic, spore-forming bacterium of the genus Clostridium. C. perfringens is ever present in nature and can be found as a normal component of decaying vegetation, marine sediment, the intestinal tract of humans and other vertebrates,... http://opm.phar.umich.edu/families.php?superfamily=116 Botulinum toxin Botulinum toxin is a protein produced by the bacterium Clostridium botulinum, and is considered the most powerful neurotoxin ever discovered. Botulinum toxin causes Botulism poisoning, a serious and life-threatening illness in humans and animals... B http://opm.phar.umich.edu/families.php?superfamily=170 Enterotoxin An enterotoxin is a protein toxin released by a microorganism in the intestine. Enterotoxins are chromosomally encoded exotoxins that are produced and secreted from several bacterial organisms. They are often heat-stable, and are of low molecular weight and water-soluble... B http://opm.phar.umich.edu/families.php?superfamily=96 Endotoxin Endotoxins are toxins associated with some Gram-negative bacteria. An "endotoxin" is a toxin that is a structural molecule of the bacteria that is recognized by the immune system.-Gram negative:... s http://opm.phar.umich.edu/families.php?superfamily=95 Bacteriocin Bacteriocins are proteinaceous toxins produced by bacteria to inhibit the growth of similar or closely related bacterial strain. They are typically considered to be narrow spectrum antibiotics, though this has been debated... s http://opm.phar.umich.edu/families.php?superfamily=164 (see microcin) Nisin Nisin is a polycyclic antibacterial peptide with 34 amino acid residues used as a food preservative. It contains the uncommon amino acids lanthionine , methyllanthionine , didehydroalanine and didehydroaminobutyric acid . These unusual amino acids are introduced by posttranslational modification... ) Gramicidin S Gramicidin S or Gramicidin Soviet is an antibiotic effective against some Gram positive and Gram negative bacteria as well as some fungi. It is a derivative of gramicidin, produced by the Gram positive bacterium Bacillus brevis... http://opm.phar.umich.edu/protein.php?pdbid=1tk2 |
Microbial toxins are the primary virulence factor Virulence factor Virulence factors are molecules expressed and secreted by pathogens that enable them to achieve the following:* colonization of a niche in the host... s for a variety of pathogenic bacteria. Some toxins, are Pore forming toxins Pore forming toxins Pore-forming toxins are protein toxins, typically , produced by bacteria, such as C.septicum and S.aureus. They are frequently cytotoxic , as they create unregulated pores in the membrane of targeted cells.-Types of PFTs:PFTs can be divided into the following subcategories:* Alpha-pore-forming... that lyse cellular membranes. Other toxins inhibit protein synthesis Protein biosynthesis Protein biosynthesis is the process in which cells build or manufacture proteins. The term is sometimes used to refer only to protein translation but more often it refers to a multi-step process, beginning with amino acid synthesis and transcription of nuclear DNA into messenger RNA, which is then... or activate second messenger pathways causing dramatic alterations to signal transduction Signal transduction Signal transduction occurs when an extracellular signaling molecule activates a cell surface receptor. In turn, this receptor alters intracellular molecules creating a response... pathways critical in maintaining a variety of cellular functions. Several bacterial toxins can act directly on the immune system Immune system An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own... , by acting as superantigen Superantigen Superantigens are a class of antigens which cause non-specific activation of T-cells resulting in oligoclonal T cell activation and massive cytokine release... s and causing massive T cell T cell T cells or T lymphocytes belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity. They can be distinguished from other lymphocytes, such as B cells and natural killer cells , by the presence of a T cell receptor on the cell surface. They are... proliferation Cell growth The term cell growth is used in the contexts of cell development and cell division . When used in the context of cell division, it refers to growth of cell populations, where one cell grows and divides to produce two "daughter cells"... , which overextends the immune system. Botulinum toxin is a neurotoxin that prevents neuro-secretory vesicles from docking/fusing with the nerve synapse Synapse In the nervous system, a synapse is a structure that permits a neuron to pass an electrical or chemical signal to another cell... plasma membrane, inhibiting neurotransmitter Neurotransmitter Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to... release. |
| Fungal Toxins |
Lipopeptide A lipopeptide is a molecule consisting of a lipid connected to a peptide. Bacteria express these molecules. They are bound by TLR 1, and other, Toll-like receptors.Certain lipopeptides are used as antibiotics.... antibiotics Surfactin Surfactin Surfactin is a very powerful surfactant commonly used as an antibiotic. It is a bacterial cyclic lipopeptide, largely prominent for its exceptional surfactant power. Its amphiphilic properties help this substance to survive in both hydrophilic and hydrophobic environments... and daptomycin Daptomycin Daptomycin is a novel lipopeptide antibiotic used in the treatment of certain infections caused by Gram-positive organisms. It is a naturally occurring compound found in the soil saprotroph Streptomyces roseosporus. Its distinct mechanism of action means that it may be useful in treating infections... http://opm.phar.umich.edu/families.php?superfamily=172 |
These peptides are characterized by the presence of an unusual amino acid, α-aminoisobutyric acid 2-Aminoisobutyric acid 2-Aminoisobutyric acid, or α-aminoisobutyric acid or α-methylalanine or 2-methylalanine, is an amino acid with the structural formula is H2N-C2-COOH. It is contained in some antibiotics of fungal origin, e.g. alamethicin and some lantibiotics. It is not one of the proteinogenic amino acids and... , and exhibit antibiotic Antibiotic An antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of... and antifungal Fungicide Fungicides are chemical compounds or biological organisms used to kill or inhibit fungi or fungal spores. Fungi can cause serious damage in agriculture, resulting in critical losses of yield, quality and profit. Fungicides are used both in agriculture and to fight fungal infections in animals... properties due to their membrane channel-forming activities. |
| Antimicrobial peptides |
Helicobacter pylori Helicobacter pylori , previously named Campylobacter pyloridis, is a Gram-negative, microaerophilic bacterium found in the stomach. It was identified in 1982 by Barry Marshall and Robin Warren, who found that it was present in patients with chronic gastritis and gastric ulcers, conditions that were... peptide http://opm.phar.umich.edu/protein.php?pdbid=1p0l Lactoferricin Lactoferricin is an amphipathic, cationic peptide with anti-microbial and anti-cancer properties. It can be generated by the pepsin-mediated digestion of lactoferrin.... B http://opm.phar.umich.edu/protein.php?pdbid=1lfc |
The modes of action by which antimicrobial peptides kill bacteria is varied and includes disrupting membranes, interfering with metabolism Metabolism Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories... , and targeting cytoplasm Cytoplasm The cytoplasm is a small gel-like substance residing between the cell membrane holding all the cell's internal sub-structures , except for the nucleus. All the contents of the cells of prokaryote organisms are contained within the cytoplasm... ic components. In contrast to many conventional antibiotics these peptides appear to be bacteriocidal instead of bacteriostatic. |
| Defensin Defensin Defensins are small cysteine-rich cationic proteins found in both vertebrates and invertebrates. They have also been reported in plants. They are, and function as, host defense peptides. They are active against bacteria, fungi and many enveloped and nonenveloped viruses. They consist of 18-45 amino... s |
Cyclotides Cyclotides Cyclotides are small disulfide rich peptides isolated from plants. Typically containing 28-37 amino acids, they are characterized by their head-to-tail cyclised peptide backbone and the interlocking arrangement of their three disulfide bonds. These combined features have been termed the cyclic... http://opm.phar.umich.edu/families.php?superfamily=64 and thionin Thionin Thionine, also known as thionine acetate or Lauth's violet, is a strongly staining metachromatic dye that are widely used for biological staining. Thionine can also be used in place of Schiff reagent in quantitative Feulgen staining of DNA. It can also be used to mediate electron transfer in... s http://opm.phar.umich.edu/families.php?superfamily=149 |
Defensins are a type of antimicrobial peptide; and are an important component of virtually all innate host defenses Innate immune system The innate immune system, also known as non-specific immune system and secondary line of defence, comprises the cells and mechanisms that defend the host from infection by other organisms in a non-specific manner... against microbial invasion. Defensins penetrate microbial cell membranes by way of electrical attraction, and form a pore in the membrane allowing efflux, which ultimately leads to the lysis of microorganisms. |
| Neuronal peptides |
|
These proteins excite neurons, evoke behavioral responses, are potent vasodilatator Vasodilation Vasodilation refers to the widening of blood vessels resulting from relaxation of smooth muscle cells within the vessel walls, particularly in the large arteries, smaller arterioles and large veins. The process is essentially the opposite of vasoconstriction, or the narrowing of blood vessels. When... s, and are responsible for contraction in many types of smooth muscle Smooth muscle Smooth muscle is an involuntary non-striated muscle. It is divided into two sub-groups; the single-unit and multiunit smooth muscle. Within single-unit smooth muscle tissues, the autonomic nervous system innervates a single cell within a sheet or bundle and the action potential is propagated by... . |
| Apoptosis Apoptosis Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation... regulators |
Bcl-2 Bcl-2 is the founding member of the Bcl-2 family of apoptosis regulator proteins encoded by the BCL2 gene. Bcl-2 derives its name from B-cell lymphoma 2, as it is the second member of a range of proteins initially described in chromosomal translocations involving chromosomes 14 and 18 in... http://opm.phar.umich.edu/families.php?superfamily=42 |
Members of the Bcl-2 family govern mitochondrial outer membrane permeability. Bcl-2 itself suppresses apoptosis in a variety of cell types including lymphocyte Lymphocyte A lymphocyte is a type of white blood cell in the vertebrate immune system.Under the microscope, lymphocytes can be divided into large lymphocytes and small lymphocytes. Large granular lymphocytes include natural killer cells... s and neuronal cells. |
See also
- Membrane proteinMembrane proteinA membrane protein is a protein molecule that is attached to, or associated with the membrane of a cell or an organelle. More than half of all proteins interact with membranes.-Function:...
s - LipoproteinLipoproteinA lipoprotein is a biochemical assembly that contains both proteins and lipids water-bound to the proteins. Many enzymes, transporters, structural proteins, antigens, adhesins, and toxins are lipoproteins...
s - Transmembrane proteins
- Antimicrobial peptides
External links
- DOLOP Genomics-oriented database of bacterial lipoproteins
- Peptaibol database
- Antimicrobial Peptide Database