MATH domain
Encyclopedia
The MATH domain, in molecular biology
, is a binding domain
that was defined originally by a region of homology
between otherwise functionally unrelated domains, the intracellular
TRAF-C domains of TRAF proteins and a C-terminal region of extracellular
meprins
A and B
.
Although apparently functionally unrelated, intracellular TRAFs and extracellular meprins share a conserved
region of about 180 residues, the meprin and TRAF homology (MATH) |domain. Meprins are mammalian tissue-specific metalloendopeptidases of the astacin
family implicated in developmental, normal and pathological
processes by hydrolysing a variety of protein
s. Various growth
factors, cytokines, and extracellular matrix
protein
s are substrates
for meprins. They are composed of five structural
domains: an N-terminal endopeptidase
domain, a MAM domain, a MATH domain, an EGF-like domain and a C-terminal transmembrane region. Meprin A and B form membrane
bound homo-tetramers whereas homo-oligomers of meprin A are secreted. A proteolytic
site adjacent to the MATH domain, only present in meprin A, allows the release of the protein from the membrane
.
TRAF proteins were first isolated through their ability to interact
with TNF receptor
s. They promote cell
survival
by the activation of downstream
protein kinase
s and, untimately, transcription factor
s of the NF-kB and AP-1 family. The TRAF proteins are composed of 3 structural domains: a RING finger in the N-terminal part of the protein, one to seven TRAF zinc finger
s in the middle and the MATH domain in the C-terminal part. The MATH domain is necessary and sufficient for self-association and receptor
interaction. Through structural analysis, two consensus sequence
s recognised by the TRAF domain have been defined: a major one, [PSAT]x[QE]E and a minor one, PxQxxD.
The structure
of the TRAF2 protein reveals a trimeric self-association of the MATH domain. The domain forms a new, light-stranded antiparallel
beta sandwich structure
. A coiled-coil
region adjacent to the MATH domain is also important for the trimerisation. The oligomerisation is essential for establishing appropriate connections to form signalling complexes with TNF receptor-1. The ligand binding surface of TRAF proteins is located in beta-strands 6 and 7.
MATH domains are found in a large number of Arabidopsis thaliana
sequences, where they often lie alongside s
, a structural domain that also promotes oligomerisation.
...
Molecular biology
Molecular biology is the branch of biology that deals with the molecular basis of biological activity. This field overlaps with other areas of biology and chemistry, particularly genetics and biochemistry...
, is a binding domain
Binding domain
A binding domain is a protein domain which binds to a specific atom or molecule, such as calcium or DNA. Upon binding, proteins may undergo a conformational change. Binding domains are essential for the function of many proteins....
that was defined originally by a region of homology
Homology (biology)
Homology forms the basis of organization for comparative biology. In 1843, Richard Owen defined homology as "the same organ in different animals under every variety of form and function". Organs as different as a bat's wing, a seal's flipper, a cat's paw and a human hand have a common underlying...
between otherwise functionally unrelated domains, the intracellular
Intracellular
Not to be confused with intercellular, meaning "between cells".In cell biology, molecular biology and related fields, the word intracellular means "inside the cell".It is used in contrast to extracellular...
TRAF-C domains of TRAF proteins and a C-terminal region of extracellular
Extracellular
In cell biology, molecular biology and related fields, the word extracellular means "outside the cell". This space is usually taken to be outside the plasma membranes, and occupied by fluid...
meprins
Meprin A
Meprin A also known as endopeptidase-2 is an enzyme that cleaves protein and peptide substrates preferentially on carboxyl side of hydrophobic residues.Meprin A is a dimer composed of the products transcribed from the following two genes:...
A and B
MEP1B
Meprin A subunit beta is a protein that in humans is encoded by the MEP1B gene.-Further reading:...
.
Although apparently functionally unrelated, intracellular TRAFs and extracellular meprins share a conserved
Conserved sequence
In biology, conserved sequences are similar or identical sequences that occur within nucleic acid sequences , protein sequences, protein structures or polymeric carbohydrates across species or within different molecules produced by the same organism...
region of about 180 residues, the meprin and TRAF homology (MATH) |domain. Meprins are mammalian tissue-specific metalloendopeptidases of the astacin
Astacin
In molecular biology, astacin is a family of metallopeptidases. These metallopeptidases belong to the MEROPS peptidase family M12, subfamily M12A...
family implicated in developmental, normal and pathological
Pathology
Pathology is the precise study and diagnosis of disease. The word pathology is from Ancient Greek , pathos, "feeling, suffering"; and , -logia, "the study of". Pathologization, to pathologize, refers to the process of defining a condition or behavior as pathological, e.g. pathological gambling....
processes by hydrolysing a variety of 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...
s. Various growth
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"...
factors, cytokines, and extracellular matrix
Extracellular 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...
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...
s are substrates
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...
for meprins. They are composed of five structural
Secondary structure
In biochemistry and structural biology, secondary structure is the general three-dimensional form of local segments of biopolymers such as proteins and nucleic acids...
domains: an N-terminal endopeptidase
Endopeptidase
Endopeptidase or endoproteinase are proteolytic peptidases that break peptide bonds of nonterminal amino acids , in contrast to exopeptidases, which break peptide bonds from their end-pieces. For this reason, endopeptidases cannot break down peptides into monomers, while exopeptidases can break...
domain, a MAM domain, a MATH domain, an EGF-like domain and a C-terminal transmembrane region. Meprin A and B form 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...
bound homo-tetramers whereas homo-oligomers of meprin A are secreted. A proteolytic
Proteolysis
Proteolysis is the directed degradation of proteins by cellular enzymes called proteases or by intramolecular digestion.-Purposes:Proteolysis is used by the cell for several purposes...
site adjacent to the MATH domain, only present in meprin A, allows the release of the protein from the 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...
.
TRAF proteins were first isolated through their ability to interact
Protein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...
with TNF receptor
Receptor (biochemistry)
In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...
s. They promote cell
Cell
-Science and technology:*Cell , the functional basic unit of life*Cell , a term used in an electronic circuit design schematics*Cell , a three-dimensional element, part of a higher-dimensional object*Cell , a scientific journal...
survival
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...
by the activation of downstream
Upstream and downstream (DNA)
In molecular biology and genetics, upstream and downstream both refer to a relative position in DNA or RNA. Each strand of DNA or RNA has a 5' end and a 3' end, so named for the carbons on the deoxyribose ring. Relative to the position on the strand, downstream is the region towards the 3' end of...
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 and, untimately, transcription factor
Transcription factor
In molecular biology and genetics, a transcription factor is a protein that binds to specific DNA sequences, thereby controlling the flow of genetic information from DNA to mRNA...
s of the NF-kB and AP-1 family. The TRAF proteins are composed of 3 structural domains: a RING finger in the N-terminal part of the protein, one to seven TRAF zinc finger
Zinc finger
Zinc fingers are small protein structural motifs that can coordinate one or more zinc ions to help stabilize their folds. They can be classified into several different structural families and typically function as interaction modules that bind DNA, RNA, proteins, or small molecules...
s in the middle and the MATH domain in the C-terminal part. The MATH domain is necessary and sufficient for self-association and receptor
Receptor (biochemistry)
In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...
interaction. Through structural analysis, two consensus sequence
Consensus sequence
In molecular biology and bioinformatics, consensus sequence refers to the most common nucleotide or amino acid at a particular position after multiple sequences are aligned. A consensus sequence is a way of representing the results of a multiple sequence alignment, where related sequences are...
s recognised by the TRAF domain have been defined: a major one, [PSAT]x[QE]E and a minor one, PxQxxD.
The structure
Secondary structure
In biochemistry and structural biology, secondary structure is the general three-dimensional form of local segments of biopolymers such as proteins and nucleic acids...
of the TRAF2 protein reveals a trimeric self-association of the MATH domain. The domain forms a new, light-stranded antiparallel
Antiparallel (biochemistry)
In biochemistry, two molecules are antiparallel if they run side-by-side in opposite directions or when both strands are complimentary to each other....
beta sandwich structure
Cis-regulatory element
A cis-regulatory element or cis-element is a region of DNA or RNA that regulates the expression of genes located on that same molecule of DNA . This term is constructed from the Latin word cis, which means "on the same side as". These cis-regulatory elements are often binding sites for one or...
. A coiled-coil
Coiled coil
A coiled coil is a structural motif in proteins, in which 2-7 alpha-helices are coiled together like the strands of a rope . Many coiled coil type proteins are involved in important biological functions such as the regulation of gene expression e.g. transcription factors...
region adjacent to the MATH domain is also important for the trimerisation. The oligomerisation is essential for establishing appropriate connections to form signalling complexes with TNF receptor-1. The ligand binding surface of TRAF proteins is located in beta-strands 6 and 7.
MATH domains are found in a large number of Arabidopsis thaliana
Arabidopsis thaliana
Arabidopsis thaliana is a small flowering plant native to Europe, Asia, and northwestern Africa. A spring annual with a relatively short life cycle, arabidopsis is popular as a model organism in plant biology and genetics...
sequences, where they often lie alongside s
BTB/POZ domain
The BTB/POZ domain is a common structural domain contained within some proteins.The BTB or POZ domain is present near the N-terminus of a fraction of zinc finger proteins and in proteins that contain the Kelch motif and a family of pox virus proteins...
, a structural domain that also promotes oligomerisation.
External links
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