6a33
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Binding and Enhanced Binding between Key Immunity Proteins TRAF6 and TIFA== | |
| + | <StructureSection load='6a33' size='340' side='right' caption='[[6a33]], [[Resolution|resolution]] 2.10Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6a33]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6A33 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6A33 FirstGlance]. <br> | ||
| + | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5zuj|5zuj]]</td></tr> | ||
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/RING-type_E3_ubiquitin_transferase RING-type E3 ubiquitin transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.2.27 2.3.2.27] </span></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6a33 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6a33 OCA], [http://pdbe.org/6a33 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6a33 RCSB], [http://www.ebi.ac.uk/pdbsum/6a33 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6a33 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[http://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> [[http://www.uniprot.org/uniprot/TIFA_HUMAN TIFA_HUMAN]] Adapter protein which mediates the IRAK1 and TRAF6 interaction following IL-1 stimulation, resulting in the downstream activation of NF-kappa-B and AP-1 pathways. Induces the oligomerization and polyubiquitination of TRAF6, which leads to the activation of TAK1 and IKK through a proteasome-independent mechanism.<ref>PMID:12566447</ref> <ref>PMID:15492226</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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 6a33" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: RING-type E3 ubiquitin transferase]] | ||
| + | [[Category: Bessho, Y]] | ||
| + | [[Category: Hsiao, T C]] | ||
| + | [[Category: Huang, W C]] | ||
| + | [[Category: Liao, J H]] | ||
| + | [[Category: Maestre-Reyna, M]] | ||
| + | [[Category: Tsai, M D]] | ||
| + | [[Category: Complex]] | ||
| + | [[Category: Protein binding]] | ||
| + | [[Category: Tifa c-terminal consensus traf-binding peptide 170-184]] | ||
| + | [[Category: Traf6]] | ||
Revision as of 06:31, 5 December 2018
Binding and Enhanced Binding between Key Immunity Proteins TRAF6 and TIFA
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