View source for 4mel


==Crystal Structure of the human USP11 DUSP-UBL domains==
<StructureSection load='4mel' size='340' side='right'caption='[[4mel]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4mel]] 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=4MEL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4MEL 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]] 2.899&#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=4mel FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mel OCA], [https://pdbe.org/4mel PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4mel RCSB], [https://www.ebi.ac.uk/pdbsum/4mel PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4mel ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/UBP11_HUMAN UBP11_HUMAN] Protease that can remove conjugated ubiquitin from target proteins and polyubiquitin chains. Inhibits the degradation of target proteins by the proteasome. Plays a role in the regulation of pathways leading to NF-kappa-B activation. Plays a role in the regulation of DNA repair after double-stranded DNA breaks.<ref>PMID:15314155</ref> <ref>PMID:17897950</ref> <ref>PMID:18408009</ref> <ref>PMID:19874889</ref> <ref>PMID:20233726</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The ubiquitin specific protease 11 (USP11) is implicated in DNA repair, viral RNA replication, and TGFbeta signaling. We report the first characterization of the USP11 domain architecture and its role in regulating the enzymatic activity. USP11 consists of an N-terminal "domain present in USPs" (DUSP) and "ubiquitin-like" (UBL) domain, together referred to as DU domains, and the catalytic domain harboring a second UBL domain. Crystal structures of the DU domains show a tandem arrangement with a shortened beta-hairpin at the two-domain interface and altered surface characteristics compared to the homologues USP4 and USP15. A conserved VEVY motif is a signature feature at the two-domain interface that shapes a potential protein interaction site. Small angle X-ray scattering and gel filtration experiments are consistent with the USP11DU domains and full-length USP11 being monomeric. Unexpectedly, we reveal, through kinetic assays of a series of deletion mutants, that the catalytic activity of USP11 is not regulated through intramolecular autoinhibition or activation by the N-terminal DU or UBL domains. Moreover, ubiquitin chain cleavage assays with all eight linkages reveal a preference for Lys63-, Lys6-, Lys33-, and Lys11-linked chains over Lys27-, Lys29-, and Lys48-linked and linear chains consistent with USP11's function in DNA repair pathways that is mediated by the protease domain. Our data support a model whereby USP11 domains outside the catalytic core domain serve as protein interaction or trafficking modules rather than a direct regulatory function of the proteolytic activity. This highlights the diversity of USPs in substrate recognition and regulation of ubiquitin deconjugation.

Structure and Catalytic Regulatory Function of Ubiquitin Specific Protease 11 N-Terminal and Ubiquitin-like Domains.,Harper S, Gratton HE, Cornaciu I, Oberer M, Scott DJ, Emsley J, Dreveny I Biochemistry. 2014 Apr 29. PMID:24724799<ref>PMID:24724799</ref>

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

==See Also==
*[[Thioesterase 3D structures|Thioesterase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Cornaciu I]]
[[Category: Dreveny I]]
[[Category: Emsley J]]
[[Category: Gratton HE]]
[[Category: Harper S]]
[[Category: Oberer M]]
[[Category: Scott DJ]]