MATH domain

MATH
solution structure of n-terminal domain of speckle-type poz protein
Identifiers
Symbol MATH
Pfam PF00917
Pfam clan CL0389
InterPro IPR002083
SCOP 1qsc
SUPERFAMILY 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 s, a structural domain that also promotes oligomerisation.[6]

References

  1. 1 2 Sunnerhagen M, Pursglove S, Fladvad M (October 2002). "The new MATH: homology suggests shared binding surfaces in meprin tetramers and TRAF trimers". FEBS Lett. 530 (1–3): 1–3. doi:10.1016/S0014-5793(02)03330-6. PMID 12387856.
  2. ↑ Marchand P, Tang J, Johnson GD, Bond JS (March 1995). "COOH-terminal proteolytic processing of secreted and membrane forms of the alpha subunit of the metalloprotease meprin A. Requirement of the I domain for processing in the endoplasmic reticulum". J. Biol. Chem. 270 (10): 5449–56. doi:10.1074/jbc.270.10.5449. PMID 7890660.
  3. ↑ Rothe M, Wong SC, Henzel WJ, Goeddel DV (August 1994). "A novel family of putative signal transducers associated with the cytoplasmic domain of the 75 kDa tumor necrosis factor receptor". Cell. 78 (4): 681–92. doi:10.1016/0092-8674(94)90532-0. PMID 8069916.
  4. 1 2 Ye H, Park YC, Kreishman M, Kieff E, Wu H (September 1999). "The structural basis for the recognition of diverse receptor sequences by TRAF2". Mol. Cell. 4 (3): 321–30. doi:10.1016/S1097-2765(00)80334-2. PMID 10518213.
  5. ↑ Park YC, Burkitt V, Villa AR, Tong L, Wu H (April 1999). "Structural basis for self-association and receptor recognition of human TRAF2". Nature. 398 (6727): 533–8. doi:10.1038/19110. PMID 10206649.
  6. ↑ Weber H, Hellmann H (2009). "Arabidopsis thaliana BTB/ POZ-MATH proteins interact with members of the ERF/AP2 transcription factor family". FEBS J. 276 (22): 6624–35. doi:10.1111/j.1742-4658.2009.07373.x. PMID 19843165.
This article incorporates text from the public domain Pfam and InterPro: IPR002083

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