“MATH domain”的意思、由来-开放百科全书

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{{cite journal |vauthors=Sunnerhagen M, Pursglove S, Fladvad M | title = The new MATH: homology suggests shared binding surfaces in meprin tetramers and TRAF trimers | journal = FEBS Lett. | volume = 530 | issue = 1-3 | pages = 1–3 |date=October 2002 | pmid = 12387856 | doi = 10.1016/S0014-5793(02)03330-6| url = }}
2. ^{{cite journal |vauthors=Marchand P, Tang J, Johnson GD, Bond JS | title = 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 | journal = J. Biol. Chem. | volume = 270 | issue = 10 | pages = 5449–56 |date=March 1995 | pmid = 7890660 | doi = 10.1074/jbc.270.10.5449| url = }}
3. ^{{cite journal |vauthors=Rothe M, Wong SC, Henzel WJ, Goeddel DV | title = A novel family of putative signal transducers associated with the cytoplasmic domain of the 75 kDa tumor necrosis factor receptor | journal = Cell | volume = 78 | issue = 4 | pages = 681–92 |date=August 1994 | pmid = 8069916 | doi = 10.1016/0092-8674(94)90532-0| url = }}
4. ^¹{{cite journal |vauthors=Ye H, Park YC, Kreishman M, Kieff E, Wu H | title = The structural basis for the recognition of diverse receptor sequences by TRAF2 | journal = Mol. Cell | volume = 4 | issue = 3 | pages = 321–30 |date=September 1999 | pmid = 10518213 | doi = 10.1016/S1097-2765(00)80334-2| url = }}
5. ^{{cite journal |vauthors=Park YC, Burkitt V, Villa AR, Tong L, Wu H | title = Structural basis for self-association and receptor recognition of human TRAF2 | journal = Nature | volume = 398 | issue = 6727 | pages = 533–8 |date=April 1999 | pmid = 10206649 | doi = 10.1038/19110 | url = }}
6. ^{{cite journal|vauthors=Weber H, Hellmann H | title=Arabidopsis thaliana BTB/ POZ-MATH proteins interact with members of the ERF/AP2 transcription factor family. | journal=FEBS J | year= 2009 | volume= 276 | issue= 22 | pages= 6624–35 | pmid=19843165 | doi=10.1111/j.1742-4658.2009.07373.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19843165 }}

References

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