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4mel

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Current revision

Crystal Structure of the human USP11 DUSP-UBL domains

Structural highlights

4mel is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.899Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.^[1] ^[2] ^[3] ^[4] ^[5]

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^[6]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Schoenfeld AR, Apgar S, Dolios G, Wang R, Aaronson SA. BRCA2 is ubiquitinated in vivo and interacts with USP11, a deubiquitinating enzyme that exhibits prosurvival function in the cellular response to DNA damage. Mol Cell Biol. 2004 Sep;24(17):7444-55. PMID:15314155 doi:http://dx.doi.org/10.1128/MCB.24.17.7444-7455.2004
↑ Yamaguchi T, Kimura J, Miki Y, Yoshida K. The deubiquitinating enzyme USP11 controls an IkappaB kinase alpha (IKKalpha)-p53 signaling pathway in response to tumor necrosis factor alpha (TNFalpha). J Biol Chem. 2007 Nov 23;282(47):33943-8. Epub 2007 Sep 26. PMID:17897950 doi:http://dx.doi.org/10.1074/jbc.M706282200
↑ Lin CH, Chang HS, Yu WC. USP11 stabilizes HPV-16E7 and further modulates the E7 biological activity. J Biol Chem. 2008 Jun 6;283(23):15681-8. doi: 10.1074/jbc.M708278200. Epub 2008, Apr 11. PMID:18408009 doi:http://dx.doi.org/10.1074/jbc.M708278200
↑ Sun W, Tan X, Shi Y, Xu G, Mao R, Gu X, Fan Y, Yu Y, Burlingame S, Zhang H, Rednam SP, Lu X, Zhang T, Fu S, Cao G, Qin J, Yang J. USP11 negatively regulates TNFalpha-induced NF-kappaB activation by targeting on IkappaBalpha. Cell Signal. 2010 Mar;22(3):386-94. doi: 10.1016/j.cellsig.2009.10.008. Epub . PMID:19874889 doi:http://dx.doi.org/10.1016/j.cellsig.2009.10.008
↑ Wiltshire TD, Lovejoy CA, Wang T, Xia F, O'Connor MJ, Cortez D. Sensitivity to poly(ADP-ribose) polymerase (PARP) inhibition identifies ubiquitin-specific peptidase 11 (USP11) as a regulator of DNA double-strand break repair. J Biol Chem. 2010 May 7;285(19):14565-71. doi: 10.1074/jbc.M110.104745. Epub 2010, Mar 15. PMID:20233726 doi:http://dx.doi.org/10.1074/jbc.M110.104745
↑ Harper S, Gratton HE, Cornaciu I, Oberer M, Scott DJ, Emsley J, Dreveny I. Structure and Catalytic Regulatory Function of Ubiquitin Specific Protease 11 N-Terminal and Ubiquitin-like Domains. Biochemistry. 2014 Apr 29. PMID:24724799 doi:http://dx.doi.org/10.1021/bi500116x

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4mel"

@@ Line 4: / Line 4: @@
 == 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='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>
+</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 ==

4mel

From Proteopedia

Current revision

Crystal Structure of the human USP11 DUSP-UBL domains

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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