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==Binding and Enhanced Binding between Key Immunity Proteins TRAF6 and TIFA==
<StructureSection load='5zuj' size='340' side='right'caption='[[5zuj]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5zuj]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ZUJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5ZUJ FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6&#8491;</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5zuj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zuj OCA], [https://pdbe.org/5zuj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5zuj RCSB], [https://www.ebi.ac.uk/pdbsum/5zuj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5zuj ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/TRAF6_HUMAN TRAF6_HUMAN] E3 ubiquitin ligase that, together with UBE2N and UBE2V1, mediates the synthesis of 'Lys-63'-linked-polyubiquitin chains conjugated to proteins, such as IKBKG, AKT1 and AKT2. Also mediates ubiquitination of free/unanchored polyubiquitin chain that leads to MAP3K7 activation. Leads to the activation of NF-kappa-B and JUN. May be essential for the formation of functional osteoclasts. Seems to also play a role in dendritic cells (DCs) maturation and/or activation. Represses c-Myb-mediated transactivation, in B-lymphocytes. Adapter protein that seems to play a role in signal transduction initiated via TNF receptor, IL-1 receptor and IL-17 receptor. Regulates osteoclast differentiation by mediating the activation of adapter protein complex 1 (AP-1) and NF-kappa-B, in response to RANK-L stimulation.<ref>PMID:8837778</ref> <ref>PMID:11057907</ref> <ref>PMID:16378096</ref> <ref>PMID:17135271</ref> <ref>PMID:18093978</ref> <ref>PMID:18758450</ref> <ref>PMID:19675569</ref> <ref>PMID:19713527</ref> <ref>PMID:12140561</ref> <ref>PMID:19465916</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Human tumor-necrosis-factor-receptor-associated factor (TRAF)-interacting protein with a forkhead-associated domain (TIFA) is a key regulator of NF-kappaB activation. It also plays a key role in the activation of innate immunity in response to bacterial infection, through heptose 1,7-bisphosphate (HBP), a metabolite of lipopolysaccharide (LPS). However, the mechanism of TIFA function is largely unexplored, except the suggestion for interacting with TRAF6. Here we provide evidence for direct binding, albeit weak, between TIFA and the TRAF domain of TRAF6, and show that the binding is enhanced for a rationally designed double mutant TIFA S174Q/M179D. The enhanced binding was also demonstrated for endogenous full-length TRAF6. Furthermore, we solved the structures of the TRAF domain complexes with the consensus TRAF-binding peptides from the C-terminus of wild-type and S174Q/M179D mutant TIFA, showing salt-bridge formation between residues 177-181 of TIFA and the binding pocket residues of the TRAF domain. Taken together, the results provide direct evidence and the structural basis for the TIFA-TRAF6 interaction, and show how this important biological function can be modulated.

Binding and Enhanced Binding between Key Immunity Proteins TRAF6 and TIFA.,Huang WC, Liao JH, Hsiao TC, Wei TW, Maestre-Reyna M, Bessho Y, Tsai MD Chembiochem. 2018 Oct 31. doi: 10.1002/cbic.201800436. PMID:30378729<ref>PMID:30378729</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5zuj" style="background-color:#fffaf0;"></div>

==See Also==
*[[TNF receptor-associated factor 3D structures|TNF receptor-associated factor 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Hsiao TC]]
[[Category: Huang WC]]
[[Category: Maestre-Reyna M]]
[[Category: Tsai MD]]