| Structural highlights
Function
[TRAF4_HUMAN] Adapter protein and signal transducer that links members of the tumor necrosis factor receptor (TNFR) family to different signaling pathways. Plays a role in the activation of NF-kappa-B and JNK, and in the regulation of cell survival and apoptosis. Regulates activation of NF-kappa-B in response to signaling through Toll-like receptors. Required for normal skeleton development, and for normal development of the respiratory tract (By similarity). Required for activation of RPS6KB1 in response to TNF signaling. Modulates TRAF6 functions.[1] [2] [3] [4] [5] [6]
Publication Abstract from PubMed
TRAF4 is a unique member of TRAF family, which is essential for innate immune response, nervous system and other systems. In addition to be an adaptor protein, TRAF4 was identified as a regulator protein in recent studies. We have determined the crystal structure of TRAF domain of TRAF4 (residues 292-466) at 2.60 A resolution by X-ray crystallography method. The trimericly assembled TRAF4 resembles a mushroom shape, containing a super helical "stalk" which is made of three right-handed intertwined alpha helixes and a C-terminal "cap", which is divided at residue L302 as a boundary. Similar to other TRAFs, both intermolecular hydrophobic interaction in super helical "stalk" and hydrogen bonds in "cap" regions contribute directly to the formation of TRAF4 trimer. However, differing from other TRAFs, there is an additional flexible loop (residues 421-426), which contains a previously identified phosphorylated site S426 exposing on the surface. This S426 was reported to be phosphorylated by IKKalpha which is the pre-requisite for TRAF4-NOD2 complex formation and thus to inhibit NOD2-induced NF-kappaB activation. Therefore, the crystal structure of TRAF4-TRAF is valuable for understanding its molecular basis for its special function and provides structural information for further studies.
Structural biology study of human TNF receptor associated factor 4 TRAF domain.,Niu F, Ru H, Ding W, Ouyang S, Liu ZJ Protein Cell. 2013 Aug 27. PMID:23982741[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Xu YC, Wu RF, Gu Y, Yang YS, Yang MC, Nwariaku FE, Terada LS. Involvement of TRAF4 in oxidative activation of c-Jun N-terminal kinase. J Biol Chem. 2002 Aug 2;277(31):28051-7. Epub 2002 May 22. PMID:12023963 doi:10.1074/jbc.M202665200
- ↑ Fleckenstein DS, Dirks WG, Drexler HG, Quentmeier H. Tumor necrosis factor receptor-associated factor (TRAF) 4 is a new binding partner for the p70S6 serine/threonine kinase. Leuk Res. 2003 Aug;27(8):687-94. PMID:12801526
- ↑ Takeshita F, Ishii KJ, Kobiyama K, Kojima Y, Coban C, Sasaki S, Ishii N, Klinman DM, Okuda K, Akira S, Suzuki K. TRAF4 acts as a silencer in TLR-mediated signaling through the association with TRAF6 and TRIF. Eur J Immunol. 2005 Aug;35(8):2477-85. PMID:16052631 doi:10.1002/eji.200526151
- ↑ Abell AN, Johnson GL. MEKK4 is an effector of the embryonic TRAF4 for JNK activation. J Biol Chem. 2005 Oct 28;280(43):35793-6. Epub 2005 Sep 12. PMID:16157600 doi:10.1074/jbc.C500260200
- ↑ Kedinger V, Alpy F, Baguet A, Polette M, Stoll I, Chenard MP, Tomasetto C, Rio MC. Tumor necrosis factor receptor-associated factor 4 is a dynamic tight junction-related shuttle protein involved in epithelium homeostasis. PLoS One. 2008;3(10):e3518. doi: 10.1371/journal.pone.0003518. Epub 2008 Oct 27. PMID:18953416 doi:10.1371/journal.pone.0003518
- ↑ Li S, Lu K, Wang J, An L, Yang G, Chen H, Cui Y, Yin X, Xie P, Xing G, He F, Zhang L. Ubiquitin ligase Smurf1 targets TRAF family proteins for ubiquitination and degradation. Mol Cell Biochem. 2010 May;338(1-2):11-7. doi: 10.1007/s11010-009-0315-y. Epub, 2009 Nov 24. PMID:19937093 doi:10.1007/s11010-009-0315-y
- ↑ Niu F, Ru H, Ding W, Ouyang S, Liu ZJ. Structural biology study of human TNF receptor associated factor 4 TRAF domain. Protein Cell. 2013 Aug 27. PMID:23982741 doi:10.1007/s13238-013-3068-z
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