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5cvo

From Proteopedia

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WDR48:USP46~ubiquitin ternary complex

Structural highlights

5cvo is a 6 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 3.885Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

WDR48_HUMAN Autosomal recessive spastic paraplegia type 60.

Function

WDR48_HUMAN Regulator of deubiquitinating complexes. Acts as a strong activator of USP1 by enhancing the USP1-mediated deubiquitination of FANCD2; USP1 being almost inactive by itself. Also activates deubiquitinating activity of complexes containing USP12 and USP46, respectively. Activates deubiquitination by increasing the catalytic turnover without increasing the affinity of deubiquitinating enzymes for the substrate. In case of infection by Herpesvirus saimiri, may play a role in vesicular transport or membrane fusion events necessary for transport to lysosomes. Induces lysosomal vesicle formation via interaction with Herpesvirus saimiri tyrosine kinase-interacting protein (TIP). Subsequently, TIP recruits tyrosine-protein kinase LCK, resulting in down-regulation of T-cell antigen receptor TCR. May play a role in generation of enlarged endosomal vesicles via interaction with TIP. In case of infection by papillomavirus HPV11, promotes the maintenance of the viral genome via its interaction with HPV11 helicase E1.^[1] ^[2] ^[3]

Publication Abstract from PubMed

Protein ubiquitination patterns are an important component of cellular signaling. The WD-repeat protein WDR48 (USP1-associated factor UAF-1) stimulates activity of ubiquitin-specific proteases USP1, USP12, and USP46. To understand how WDR48 exerts its effect on the USP scaffold, we determined structures of the ternary WDR48:USP46:ubiquitin complex. WDR48 interacts with the USP46 fingers subdomain via a relatively small, highly polar surface on the top center of the WDR48 beta propeller. In addition, WDR48 has a novel ancillary domain and a C-terminal SUMO-like domain encircling the USP46-bound ubiquitin. Mutation of residues involved in the WDR48:USP46 interaction abrogated both binding and deubiquitinase activity of the complex. An analogous mutation in USP1 similarly blocked WDR48-dependent activation. Our data suggest a possible mechanism of deubiquitinase stimulation via stabilization and prolonged residence time of substrate. The unprecedented mode of interaction between the USP fingers domain and the WD-repeat beta propeller serves as a prototypical example for this family of deubiquitinases.

Structural Insights into WD-Repeat 48 Activation of Ubiquitin-Specific Protease 46.,Yin J, Schoeffler AJ, Wickliffe K, Newton K, Starovasnik MA, Dueber EC, Harris SF Structure. 2015 Sep 12. pii: S0969-2126(15)00359-7. doi:, 10.1016/j.str.2015.08.010. PMID:26388029^[4]

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

References

↑ Park J, Lee BS, Choi JK, Means RE, Choe J, Jung JU. Herpesviral protein targets a cellular WD repeat endosomal protein to downregulate T lymphocyte receptor expression. Immunity. 2002 Aug;17(2):221-33. PMID:12196293
↑ Cohn MA, Kowal P, Yang K, Haas W, Huang TT, Gygi SP, D'Andrea AD. A UAF1-containing multisubunit protein complex regulates the Fanconi anemia pathway. Mol Cell. 2007 Dec 14;28(5):786-97. PMID:18082604 doi:http://dx.doi.org/10.1016/j.molcel.2007.09.031
↑ Cohn MA, Kee Y, Haas W, Gygi SP, D'Andrea AD. UAF1 is a subunit of multiple deubiquitinating enzyme complexes. J Biol Chem. 2009 Feb 20;284(8):5343-51. doi: 10.1074/jbc.M808430200. Epub 2008, Dec 15. PMID:19075014 doi:http://dx.doi.org/10.1074/jbc.M808430200
↑ Yin J, Schoeffler AJ, Wickliffe K, Newton K, Starovasnik MA, Dueber EC, Harris SF. Structural Insights into WD-Repeat 48 Activation of Ubiquitin-Specific Protease 46. Structure. 2015 Sep 12. pii: S0969-2126(15)00359-7. doi:, 10.1016/j.str.2015.08.010. PMID:26388029 doi:http://dx.doi.org/10.1016/j.str.2015.08.010

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5cvo"

Categories: Homo sapiens | Large Structures | Harris SF | Yin J

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[5cvo]] is a 6 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=5CVO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5CVO FirstGlance]. <br>
-</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>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.885&#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=5cvo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5cvo OCA], [https://pdbe.org/5cvo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5cvo RCSB], [https://www.ebi.ac.uk/pdbsum/5cvo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5cvo ProSAT]</span></td></tr>
 </table>

5cvo

From Proteopedia

Current revision

WDR48:USP46~ubiquitin ternary complex

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

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