View source for 5lru


==Structure of Cezanne/OTUD7B OTU domain==
<StructureSection load='5lru' size='340' side='right'caption='[[5lru]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5lru]] is a 1 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=5LRU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5LRU 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]] 2.2&#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=5lru FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lru OCA], [https://pdbe.org/5lru PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5lru RCSB], [https://www.ebi.ac.uk/pdbsum/5lru PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5lru ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/OTU7B_HUMAN OTU7B_HUMAN] Negative regulator of the non-canonical NF-kappa-B pathway that acts by mediating deubiquitination of TRAF3, an inhibitor of the NF-kappa-B pathway, thereby acting as a negative regulator of B-cell responses. In response to non-canonical NF-kappa-B stimuli, deubiquitinates 'Lys-48'-linked polyubiquitin chains of TRAF3, preventing TRAF3 proteolysis and over-activation of non-canonical NF-kappa-B. Negatively regulates mucosal immunity against infections. Mediates deubiquitination of EGFR. Has deubiquitinating activity toward 'Lys-11', 'Lys-48' or 'Lys-63'-linked polyubiquitin chains. In vitro, has preference for 'Lys-11'-linked polyubiquitin chains; however such data are unsure in vivo. Hydrolyzes both linear and branched forms of polyubiquitin.<ref>PMID:11463333</ref> <ref>PMID:12682062</ref> <ref>PMID:18178551</ref> <ref>PMID:20622874</ref> <ref>PMID:22179831</ref> <ref>PMID:23827681</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The post-translational modification of proteins with polyubiquitin regulates virtually all aspects of cell biology. Eight distinct chain linkage types co-exist in polyubiquitin and are independently regulated in cells. This 'ubiquitin code' determines the fate of the modified protein. Deubiquitinating enzymes of the ovarian tumour (OTU) family regulate cellular signalling by targeting distinct linkage types within polyubiquitin, and understanding their mechanisms of linkage specificity gives fundamental insights into the ubiquitin system. Here we reveal how the deubiquitinase Cezanne (also known as OTUD7B) specifically targets Lys11-linked polyubiquitin. Crystal structures of Cezanne alone and in complex with monoubiquitin and Lys11-linked diubiquitin, in combination with hydrogen-deuterium exchange mass spectrometry, enable us to reconstruct the enzymatic cycle in great detail. An intricate mechanism of ubiquitin-assisted conformational changes activates the enzyme, and while all chain types interact with the enzymatic S1 site, only Lys11-linked chains can bind productively across the active site and stimulate catalytic turnover. Our work highlights the plasticity of deubiquitinases and indicates that new conformational states can occur when a true substrate, such as diubiquitin, is bound at the active site.

Molecular basis of Lys11-polyubiquitin specificity in the deubiquitinase Cezanne.,Mevissen TE, Kulathu Y, Mulder MP, Geurink PP, Maslen SL, Gersch M, Elliott PR, Burke JE, van Tol BD, Akutsu M, El Oualid F, Kawasaki M, Freund SM, Ovaa H, Komander D Nature. 2016 Oct 12;538(7625):402-405. doi: 10.1038/nature19836. PMID:27732584<ref>PMID:27732584</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5lru" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Akutsu M]]
[[Category: Burke JE]]
[[Category: El Oualid F]]
[[Category: Elliott PR]]
[[Category: Freund SMV]]
[[Category: Gersch M]]
[[Category: Geurink PP]]
[[Category: Kawasaki M]]
[[Category: Komander D]]
[[Category: Kulathu Y]]
[[Category: Maslen SL]]
[[Category: Mevissen TET]]
[[Category: Mulder MPC]]
[[Category: Ovaa H]]
[[Category: Van Tol BDM]]