View source for 4ym4


==Truncated Human TIFA in complex with its Thr9 phosphorylated N-terminal peptide 1-15==
<StructureSection load='4ym4' size='340' side='right'caption='[[4ym4]], [[Resolution|resolution]] 3.12&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4ym4]] 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=4YM4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4YM4 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]] 3.12&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></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=4ym4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ym4 OCA], [https://pdbe.org/4ym4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ym4 RCSB], [https://www.ebi.ac.uk/pdbsum/4ym4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ym4 ProSAT]</span></td></tr>
</table>
== Function ==
[https://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 ==
Forkhead-associated (FHA) domain is the only signaling domain that recognizes phosphothreonine (pThr) specifically. TRAF-interacting protein with an FHA domain (TIFA) was shown to be involved in immune responses by binding with TRAF2 and TRAF6. We recently reported that TIFA is a dimer in solution and that, upon stimulation by TNF-alpha, TIFA is phosphorylated at Thr9, which triggers TIFA oligomerization via pThr9-FHA domain binding and activates nuclear factor kappaB (NF-kappaB). However, the structural mechanism for the functionally important TIFA oligomerization remains to be established. While FHA domain-pThr binding is known to mediate protein dimerization, its role in oligomerization has not been demonstrated at the structural level. Here we report the crystal structures of TIFA (residues 1-150, with the unstructured C-terminal tail truncated) and its complex with the N-terminal pThr9 peptide (residues 1-15), which show unique features in the FHA structure (intrinsic dimer and extra beta-strand) and in its interaction with the pThr peptide (with residues preceding rather than following pThr). These structural features support previous and additional functional analyses. Furthermore, the structure of the complex suggests that the pThr9-FHA domain interaction can occur only between different sets of dimers rather than between the two protomers within a dimer, providing the structural mechanism for TIFA oligomerization. Our results uncover the mechanism of FHA domain-mediated oligomerization in a key step of immune responses and expand the paradigm of FHA domain structure and function.

Uncovering the Mechanism of Forkhead-Associated Domain-Mediated TIFA Oligomerization That Plays a Central Role in Immune Responses.,Weng JH, Hsieh YC, Huang CC, Wei TY, Lim LH, Chen YH, Ho MR, Wang I, Huang KF, Chen CJ, Tsai MD Biochemistry. 2015 Oct 13;54(40):6219-29. doi: 10.1021/acs.biochem.5b00500. Epub , 2015 Oct 1. PMID:26389808<ref>PMID:26389808</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4ym4" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Chen CJ]]
[[Category: Chen ESW]]
[[Category: Hsieh YC]]
[[Category: Huang CCF]]
[[Category: Huang KF]]
[[Category: Tsai MD]]
[[Category: Wei TYW]]
[[Category: Weng JH]]
[[Category: Wu PYG]]