SM00061

meprin and TRAF homology

SMART entry
Member databaseSMART
SMART typedomain
Short nameMATH

Description
Imported from IPR002083

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 (see
[prositedoc:PDOC00604]
), a MATH domain, an EGF-like domain (see
[prositedoc:PDOC00021]
) and a C-terminal transmembrane region. Meprin A and B form membrane bound homotetramer whereas homooligomers of meprin A are secreted. A proteolitic 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 by their ability to interact with TNF receptors
[3]
. They promote cell survival by the activation of downstream protein kinases and, finally, transcription factors of the NF-kB and AP-1 family. The TRAF proteins are composed of 3 structural domains: a RING finger (see
[prositedoc:PDOC00449]
) in the N-terminal part of the protein, one to seven TRAF zinc fingers (see
[prositedoc:PDOC50145]
) 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. From the structural analysis two consensus sequence 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 β-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 β-strands 6 and 7
[4]
.

References
Imported from IPR002083

1.The new MATH: homology suggests shared binding surfaces in meprin tetramers and TRAF trimers. Sunnerhagen M, Pursglove S, Fladvad M. FEBS Lett. 530, 1-3, (2002). View articlePMID: 12387856

2.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. Marchand P, Tang J, Johnson GD, Bond JS. J. Biol. Chem. 270, 5449-56, (1995). View articlePMID: 7890660

3.A novel family of putative signal transducers associated with the cytoplasmic domain of the 75 kDa tumor necrosis factor receptor. Rothe M, Wong SC, Henzel WJ, Goeddel DV. Cell 78, 681-92, (1994). View articlePMID: 8069916

4.The structural basis for the recognition of diverse receptor sequences by TRAF2. Ye H, Park YC, Kreishman M, Kieff E, Wu H. Mol. Cell 4, 321-30, (1999). View articlePMID: 10518213

5.Structural basis for self-association and receptor recognition of human TRAF2. Park YC, Burkitt V, Villa AR, Tong L, Wu H. Nature 398, 533-8, (1999). View articlePMID: 10206649

Further reading

6. A novel mechanism of TRAF signaling revealed by structural and functional analyses of the TRADD-TRAF2 interaction. Park YC, Ye H, Hsia C, Segal D, Rich RL, Liou HC, Myszka DG, Wu H. Cell 101, 777-87, (2000). View articlePMID: 10892748

7. Molecular basis for CD40 signaling mediated by TRAF3. Ni CZ, Welsh K, Leo E, Chiou CK, Wu H, Reed JC, Ely KR. Proc. Natl. Acad. Sci. U.S.A. 97, 10395-9, (2000). View articlePMID: 10984535

8. Downstream regulator TANK binds to the CD40 recognition site on TRAF3. Li C, Ni CZ, Havert ML, Cabezas E, He J, Kaiser D, Reed JC, Satterthwait AC, Cheng G, Ely KR. Structure 10, 403-11, (2002). View articlePMID: 12005438

Integrated to
External Links
This website requires cookies, and the limited processing of your personal data in order to function. By using the site you are agreeing to this as outlined in our Privacy Notice and Terms of Use.