Proteoglycan
Encyclopedia
Proteoglycans are protein
s that are heavily glycosylated
. The basic proteoglycan unit consists of a "core protein
" with one or more covalently
attached glycosaminoglycan
(GAG) chain(s). The point of attachment is a Ser residue to which the glycosaminoglycan is joined through a tetrasaccharide bridge (For example: chondroitin sulfate
-GlcA-Gal-Gal-Xyl-PROTEIN). The Ser residue is generally in the sequence -Ser-Gly-X-Gly- (where X can be any amino acid residue), although not every protein with this sequence has an attached glycosaminoglycan. The chains are long, linear carbohydrate polymers that are negatively charged under physiological conditions, due to the occurrence of sulfate
and uronic acid
groups. Proteoglycans occur in the connective tissue
.
).
Types include:
Certain members are considered members of the "small leucine-rich proteoglycan family" (SLRP). These include decorin
, biglycan
, fibromodulin and lumican.
, the "filler" substance existing between cell
s in an organism. Here they form large complexes, both to other proteoglycans, to hyaluronan
and to fibrous matrix proteins (such as collagen
). They are also involved in binding cations (such as sodium
, potassium
and calcium
) and water
, and also regulating the movement of molecules through the matrix. Evidence also shows they can affect the activity and stability of proteins and signalling molecules within the matrix. Individual functions of proteoglycans can be attributed to either the protein core or the attached GAG chain and serve as lubricants.
s and translocated
into the lumen of the rough endoplasmic reticulum. Glycosylation of the proteoglycan occurs in the Golgi apparatus
in multiple enzymatic
steps. First a special link tetrasaccharide is attached to a serine
side chain on the core protein to serve as a primer for polysaccharide growth. Then sugars are added one at a time by glycosyl transferase. The completed proteoglycan is then exported in secretory vesicle
s to the extracellular matrix of the cell.
s, called mucopolysaccharidoses. The inactivity of specific lysozomal
enzymes that normally degrade glycosaminoglycans leads to the accumulation of proteoglycans within cells. This leads to a variety of disease symptoms, depending upon the type of proteoglycan that is not degraded.
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 are heavily glycosylated
Glycosylation
Glycosylation is the reaction in which a carbohydrate, i.e. a glycosyl donor, is attached to a hydroxyl or other functional group of another molecule . In biology glycosylation refers to the enzymatic process that attaches glycans to proteins, lipids, or other organic molecules...
. The basic proteoglycan unit consists of a "core protein
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...
" with one or more covalently
Covalent bond
A covalent bond is a form of chemical bonding that is characterized by the sharing of pairs of electrons between atoms. The stable balance of attractive and repulsive forces between atoms when they share electrons is known as covalent bonding....
attached glycosaminoglycan
Glycosaminoglycan
Glycosaminoglycans or mucopolysaccharides are long unbranched polysaccharides consisting of a repeating disaccharide unit. The repeating unit consists of a hexose or a hexuronic acid, linked to a hexosamine .-Production:Protein cores made in the rough endoplasmic reticulum are posttranslationally...
(GAG) chain(s). The point of attachment is a Ser residue to which the glycosaminoglycan is joined through a tetrasaccharide bridge (For example: chondroitin sulfate
Chondroitin sulfate
Chondroitin sulfate is a sulfated glycosaminoglycan composed of a chain of alternating sugars . It is usually found attached to proteins as part of a proteoglycan. A chondroitin chain can have over 100 individual sugars, each of which can be sulfated in variable positions and quantities...
-GlcA-Gal-Gal-Xyl-PROTEIN). The Ser residue is generally in the sequence -Ser-Gly-X-Gly- (where X can be any amino acid residue), although not every protein with this sequence has an attached glycosaminoglycan. The chains are long, linear carbohydrate polymers that are negatively charged under physiological conditions, due to the occurrence of sulfate
Sulfate
In inorganic chemistry, a sulfate is a salt of sulfuric acid.-Chemical properties:...
and uronic acid
Uronic acid
thumb|300px|The [[Fischer projection]]s of [[glucose]] and [[glucuronic acid]]. Glucose's terminal carbon's hydroxyl group has been oxidized to a [[carboxylic acid]]....
groups. Proteoglycans occur in the connective tissue
Connective tissue
"Connective tissue" is a fibrous tissue. It is one of the four traditional classes of tissues . Connective Tissue is found throughout the body.In fact the whole framework of the skeleton and the different specialized connective tissues from the crown of the head to the toes determine the form of...
.
Types
Proteoglycans can be categorised depending upon the nature of their glycosaminoglycan chains. Proteoglycans can also be categorised by size (kDaAtomic mass unit
The unified atomic mass unit or dalton is a unit that is used for indicating mass on an atomic or molecular scale. It is defined as one twelfth of the rest mass of an unbound neutral atom of carbon-12 in its nuclear and electronic ground state, and has a value of...
).
Types include:
| Glycosaminoglycans | Small proteoglycans | Large proteoglycans |
|---|---|---|
| chondroitin sulfate Chondroitin sulfate Chondroitin sulfate is a sulfated glycosaminoglycan composed of a chain of alternating sugars . It is usually found attached to proteins as part of a proteoglycan. A chondroitin chain can have over 100 individual sugars, each of which can be sulfated in variable positions and quantities... /dermatan sulfate Dermatan sulfate Dermatan sulfate is a glycosaminoglycan found mostly in skin, but also in blood vessels, heart valves, tendons, and lungs.... |
decorin Decorin Decorin is a proteoglycan on average 90 - 140 kilodaltons in size.It belongs to the small leucine-rich proteoglycan family and consists of a protein core containing leucine repeats with a glycosaminoglycan chain consisting of either chondroitin sulfate or dermatan sulfate .Decorin is a small... , kDa=36 biglycan Biglycan Biglycan is a small leucine-rich repeat proteoglycan which is found in a variety of extracellular matrix tissues, including bone, cartilage and tendon... , kDa=38 |
versican Versican Versican, also known as VCAN, is a large extracellular matrix proteoglycan that is present in a variety of human tissues. It is encoded by the VCAN gene.... , kDa=260-370, present in many adult tissues including blood vessels and skin |
| heparan sulfate Heparan sulfate Heparan sulfate is a linear polysaccharide found in all animal tissues. It occurs as a proteoglycan in which two or three HS chains are attached in close proximity to cell surface or extracellular matrix proteins... /chondroitin sulfate Chondroitin sulfate Chondroitin sulfate is a sulfated glycosaminoglycan composed of a chain of alternating sugars . It is usually found attached to proteins as part of a proteoglycan. A chondroitin chain can have over 100 individual sugars, each of which can be sulfated in variable positions and quantities... |
testican Testican Testican is a type of proteoglycan.Types include:* SPOCK1 * SPOCK2... , kDa=44 |
perlecan Perlecan Perlecan also known as basement membrane-specific heparan sulfate proteoglycan core protein or heparan sulfate proteoglycan 2 , is a protein that in humans is encoded by the HSPG2 gene.... , kDa=400-470 |
| chondroitin sulfate Chondroitin sulfate Chondroitin sulfate is a sulfated glycosaminoglycan composed of a chain of alternating sugars . It is usually found attached to proteins as part of a proteoglycan. A chondroitin chain can have over 100 individual sugars, each of which can be sulfated in variable positions and quantities... |
neurocan, kDa=136 aggrecan Aggrecan Aggrecan also known as cartilage-specific proteoglycan core protein or chondroitin sulfate proteoglycan 1 is a protein that in humans is encoded by the ACAN gene. This gene is a member of the aggrecan/versican proteoglycan family... , kDa=220, the major proteoglycan in cartilage Cartilage Cartilage is a flexible connective tissue found in many areas in the bodies of humans and other animals, including the joints between bones, the rib cage, the ear, the nose, the elbow, the knee, the ankle, the bronchial tubes and the intervertebral discs... |
|
| keratan sulfate Keratan sulfate Keratan sulfate , also called keratosulfate, is any of several sulfated glycosaminoglycans that have been found especially in the cornea, cartilage, and bone. It is also synthesized in the central nervous system where it participates both in development and in the glial scar formation following an... |
fibromodulin, kDa=42 lumican, kDa=38 |
Certain members are considered members of the "small leucine-rich proteoglycan family" (SLRP). These include decorin
Decorin
Decorin is a proteoglycan on average 90 - 140 kilodaltons in size.It belongs to the small leucine-rich proteoglycan family and consists of a protein core containing leucine repeats with a glycosaminoglycan chain consisting of either chondroitin sulfate or dermatan sulfate .Decorin is a small...
, biglycan
Biglycan
Biglycan is a small leucine-rich repeat proteoglycan which is found in a variety of extracellular matrix tissues, including bone, cartilage and tendon...
, fibromodulin and lumican.
Function
Proteoglycans are a major component of the animal extracellular matrixExtracellular matrix
In biology, the extracellular matrix is the extracellular part of animal tissue that usually provides structural support to the animal cells in addition to performing various other important functions. The extracellular matrix is the defining feature of connective tissue in animals.Extracellular...
, the "filler" substance existing between cell
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
s in an organism. Here they form large complexes, both to other proteoglycans, to hyaluronan
Hyaluronan
Hyaluronan is an anionic, nonsulfated glycosaminoglycan distributed widely throughout connective, epithelial, and neural tissues...
and to fibrous matrix proteins (such as collagen
Collagen
Collagen is a group of naturally occurring proteins found in animals, especially in the flesh and connective tissues of mammals. It is the main component of connective tissue, and is the most abundant protein in mammals, making up about 25% to 35% of the whole-body protein content...
). They are also involved in binding cations (such as sodium
Sodium
Sodium is a chemical element with the symbol Na and atomic number 11. It is a soft, silvery-white, highly reactive metal and is a member of the alkali metals; its only stable isotope is 23Na. It is an abundant element that exists in numerous minerals, most commonly as sodium chloride...
, potassium
Potassium
Potassium is the chemical element with the symbol K and atomic number 19. Elemental potassium is a soft silvery-white alkali metal that oxidizes rapidly in air and is very reactive with water, generating sufficient heat to ignite the hydrogen emitted in the reaction.Potassium and sodium are...
and 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...
) and water
Water
Water is a chemical substance with the chemical formula H2O. A water molecule contains one oxygen and two hydrogen atoms connected by covalent bonds. Water is a liquid at ambient conditions, but it often co-exists on Earth with its solid state, ice, and gaseous state . Water also exists in a...
, and also regulating the movement of molecules through the matrix. Evidence also shows they can affect the activity and stability of proteins and signalling molecules within the matrix. Individual functions of proteoglycans can be attributed to either the protein core or the attached GAG chain and serve as lubricants.
Synthesis
The protein component of proteoglycans is synthesized by ribosomeRibosome
A ribosome is a component of cells that assembles the twenty specific amino acid molecules to form the particular protein molecule determined by the nucleotide sequence of an RNA molecule....
s and translocated
Translocon
The translocon is the complex of proteins associated with the translocation of nascent polypeptides across membranes. In eukaryotes the polypeptides are transported into the interior space of the endoplasmic reticulum from the cytosol...
into the lumen of the rough endoplasmic reticulum. Glycosylation of the proteoglycan occurs in the Golgi apparatus
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....
in multiple enzymatic
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...
steps. First a special link tetrasaccharide is attached to a serine
Serine
Serine is an amino acid with the formula HO2CCHCH2OH. It is one of the proteinogenic amino acids. By virtue of the hydroxyl group, serine is classified as a polar amino acid.-Occurrence and biosynthesis:...
side chain on the core protein to serve as a primer for polysaccharide growth. Then sugars are added one at a time by glycosyl transferase. The completed proteoglycan is then exported in secretory 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...
s to the extracellular matrix of the cell.
Proteoglycans and disease
An inability to break down proteoglycans is characteristic of a group of genetic disorderGenetic disorder
A genetic disorder is an illness caused by abnormalities in genes or chromosomes, especially a condition that is present from before birth. Most genetic disorders are quite rare and affect one person in every several thousands or millions....
s, called mucopolysaccharidoses. The inactivity of specific lysozomal
Lysosome
thumb|350px|Schematic of typical animal cell, showing subcellular components. [[Organelle]]s: [[nucleoli]] [[cell nucleus|nucleus]] [[ribosomes]] [[vesicle |vesicle]] rough [[endoplasmic reticulum]]...
enzymes that normally degrade glycosaminoglycans leads to the accumulation of proteoglycans within cells. This leads to a variety of disease symptoms, depending upon the type of proteoglycan that is not degraded.