View source for 8eaz


==HOIL-1/E2-Ub/Ub transthiolation complex==
<StructureSection load='8eaz' size='340' side='right'caption='[[8eaz]], [[Resolution|resolution]] 3.08&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8eaz]] is a 8 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=8EAZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8EAZ 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]] 3.08&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</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=8eaz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8eaz OCA], [https://pdbe.org/8eaz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8eaz RCSB], [https://www.ebi.ac.uk/pdbsum/8eaz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8eaz 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 ==
The RING-between-RING (RBR) E3 ubiquitin ligase family in humans comprises 14 members and is defined by a two-step catalytic mechanism in which ubiquitin is first transferred from an E2 ubiquitin-conjugating enzyme to the RBR active site and then to the substrate. To define the core features of this catalytic mechanism, we here structurally and biochemically characterise the two RBRs HOIL-1 and RNF216. Crystal structures of both enzymes in their RBR/E2-Ub/Ub transthiolation complexes capturing the first catalytic step, together with complementary functional experiments, reveal the defining features of the RBR catalytic mechanism. RBRs catalyse ubiquitination via a conserved transthiolation complex structure that enables efficient E2-to-RBR ubiquitin transfer. Our data also highlight a conserved RBR allosteric activation mechanism by distinct ubiquitin linkages that suggests RBRs employ a feed-forward mechanism. We finally identify that the HOIL-1 RING2 domain contains an unusual Zn2/Cys6 binuclear cluster that is required for catalytic activity and substrate ubiquitination.

The unifying catalytic mechanism of the RING-between-RING E3 ubiquitin ligase family.,Wang XS, Cotton TR, Trevelyan SJ, Richardson LW, Lee WT, Silke J, Lechtenberg BC Nat Commun. 2023 Jan 11;14(1):168. doi: 10.1038/s41467-023-35871-z. PMID:36631489<ref>PMID:36631489</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8eaz" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Cotton TR]]
[[Category: Lechtenberg BC]]
[[Category: Wang XS]]