View source for 4dbg


==Crystal structure of HOIL-1L-UBL complexed with a HOIP-UBA derivative==
<StructureSection load='4dbg' size='340' side='right'caption='[[4dbg]], [[Resolution|resolution]] 2.71&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4dbg]] 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=4DBG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DBG 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]] 2.71&#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=4dbg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dbg OCA], [https://pdbe.org/4dbg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4dbg RCSB], [https://www.ebi.ac.uk/pdbsum/4dbg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4dbg ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/HOIL1_HUMAN HOIL1_HUMAN] Autoinflammatory syndrome with pyogenic bacterial infection and amylopectinosis. 
== Function ==
[https://www.uniprot.org/uniprot/HOIL1_HUMAN HOIL1_HUMAN] E3 ubiquitin-protein ligase, which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, such as UBE2L3/UBCM4, and then transfers it to substrates. Functions as an E3 ligase for oxidized IREB2 and both heme and oxygen are necessary for IREB2 ubiquitination. Promotes ubiquitination of TAB2 and IRF3 and their degradation by the proteasome. Component of the LUBAC complex which conjugates linear ('Met-1'-linked) polyubiquitin chains to substrates and plays a key role in NF-kappa-B activation and regulation of inflammation. LUBAC conjugates linear polyubiquitin to IKBKG and RIPK1 and is involved in activation of the canonical NF-kappa-B and the JNK signaling pathways. Linear ubiquitination mediated by the LUBAC complex interferes with TNF-induced cell death and thereby prevents inflammation. LUBAC is proposed to be recruited to the TNF-R1 signaling complex (TNF-RSC) following polyubiquitination of TNF-RSC components by BIRC2 and/or BIRC3 and to conjugate linear polyubiquitin to IKBKG and possibly other components contributing to the stability of the complex. Together with FAM105B/otulin, the LUBAC complex regulates the canonical Wnt signaling during angiogenesis. Binds polyubiquitin of different linkage types.<ref>PMID:12629548</ref> <ref>PMID:17006537</ref> <ref>PMID:17449468</ref> <ref>PMID:18711448</ref> <ref>PMID:20005846</ref> <ref>PMID:19136968</ref> <ref>PMID:21455173</ref> <ref>PMID:21455180</ref> <ref>PMID:21455181</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
HOIL-1L and its binding partner HOIP are essential components of the E3-ligase complex that generates linear ubiquitin (Ub) chains, which are critical regulators of NF-kappaB activation. Using crystallographic and mutational approaches, we characterize the unexpected structural basis for the specific interaction between the Ub-like domain (UBL) of HOIL-1L and the Ub-associated domain (UBA) of HOIP. Our data indicate the functional significance of this non-canonical mode of UBA-UBL interaction in E3 complex formation and subsequent NF-kappaB activation. This study highlights the versatility and specificity of protein-protein interactions involving Ub/UBLs and their cognate proteins.

A non-canonical UBA-UBL interaction forms the linear-ubiquitin-chain assembly complex.,Yagi H, Ishimoto K, Hiromoto T, Fujita H, Mizushima T, Uekusa Y, Yagi-Utsumi M, Kurimoto E, Noda M, Uchiyama S, Tokunaga F, Iwai K, Kato K EMBO Rep. 2012 Mar 20. doi: 10.1038/embor.2012.24. PMID:22430200<ref>PMID:22430200</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4dbg" style="background-color:#fffaf0;"></div>

==See Also==
*[[Ubiquitin protein ligase 3D structures|Ubiquitin protein ligase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Hiromoto T]]
[[Category: Kato K]]
[[Category: Kurimoto E]]
[[Category: Mizushima T]]
[[Category: Yagi H]]