4emo: Difference between revisions
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==Crystal structure of the PH domain of SHARPIN== | |||
<StructureSection load='4emo' size='340' side='right'caption='[[4emo]], [[Resolution|resolution]] 2.00Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4emo]] is a 4 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=4EMO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4EMO 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]] 2Å</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></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=4emo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4emo OCA], [https://pdbe.org/4emo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4emo RCSB], [https://www.ebi.ac.uk/pdbsum/4emo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4emo ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/SHRPN_HUMAN SHRPN_HUMAN] Component of the LUBAC complex which conjugates linear polyubiquitin chains in a head-to-tail manner 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.<ref>PMID:21455173</ref> <ref>PMID:21455180</ref> <ref>PMID:21455181</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
E3 ubiquitin ligase complex called LUBAC (linear ubiquitin chain assembly complex) that catalyses the formation of linear ubiquitin chains and regulates immune and apoptopic signalling pathways. The C-terminal half of SHARPIN contains ubiquitin like domain (UBL) and Npl4-zinc finger (NZF) domains that mediate the interaction with the LUBAC subunit HOIP and ubiquitin, respectively. In contrast, the N-terminal region does not show any homology with known protein interaction domains but has been suggested to be responsible for self-association of SHARPIN, presumably via a coiled-coil region. We have determined the crystal structure of the N-terminal portion of SHARPIN, which adopts the highly conserved pleckstrin homology (PH) superfold that is often used as a scaffold to create protein interaction modules. We show that in SHARPIN this domain does not appear to be used as a ligand recognition domain since it lacks many of the surface properties that are present in other PH fold-based interaction modules. Instead it acts as a dimerization module extending the functional applications of this superfold. | |||
Structural analysis of SHARPIN, a subunit of a large multi-protein E3 ubiquitin ligase, reveals a novel dimerization function for the pleckstrin homology superfold.,Stieglitz B, Haire LF, Dikic I, Rittinger K J Biol Chem. 2012 May 1. PMID:22549881<ref>PMID:22549881</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4emo" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
== | __TOC__ | ||
< | </StructureSection> | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Dikic | [[Category: Large Structures]] | ||
[[Category: Haire | [[Category: Dikic I]] | ||
[[Category: Rittinger | [[Category: Haire LF]] | ||
[[Category: Stieglitz | [[Category: Rittinger K]] | ||
[[Category: Stieglitz B]] | |||