| Symbol: | MATH |
| MATH | |
| Pfam: | PF00917 |
| Pfam Clan: | CL0389 |
| Interpro: | IPR002083 |
| Scop: | 1qsc |
| Cdd: | cd00121 |
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.[1] Meprins are mammalian tissue-specific metalloendopeptidases of the astacin family implicated in developmental, normal and pathological processes by hydrolysing a variety of proteins. Various growth factors, cytokines, and extracellular matrix proteins 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.[2]
TRAF proteins were first isolated through their ability to interact with TNF receptors.[3] They promote cell survival by the activation of downstream protein kinases and, ultimately, transcription factors of the NF-κB 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 fingers in the middle and the MATH domain in the C-terminal part.[1] The MATH domain is necessary and sufficient for self-association and receptor interaction. Through structural analysis, two consensus sequences recognised by the TRAF domain have been defined: a major one, [PSAT]x[QE]E and a minor one, PxQxxD.[4]
The structure of the TRAF2 protein reveals a trimeric self-association of the MATH domain.[5] 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.[4]
MATH domains are found in a large number of Arabidopsis thaliana sequences, where they often lie alongside BTB/POZ domains, a structural domain that also promotes oligomerisation.[6]
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