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4uem

From Proteopedia

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Current revision

UCH-L5 in complex with the RPN13 DEUBAD domain

Structural highlights

4uem 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 2.82Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

UCHL5_HUMAN Protease that specifically cleaves 'Lys-48'-linked polyubiquitin chains. Deubiquitinating enzyme associated with the 19S regulatory subunit of the 26S proteasome. Putative regulatory component of the INO80 complex; however is inactive in the INO80 complex and is activated by a transient interaction of the INO80 complex with the proteasome via ADRM1.^[1] ^[2]

Publication Abstract from PubMed

Deubiquitinating enzymes (DUBs) control vital processes in eukaryotes by hydrolyzing ubiquitin adducts. Their activities are tightly regulated, but the mechanisms remain elusive. In particular, the DUB UCH-L5 can be either activated or inhibited by conserved regulatory proteins RPN13 and INO80G, respectively. Here we show how the DEUBAD domain in RPN13 activates UCH-L5 by positioning its C-terminal ULD domain and crossover loop to promote substrate binding and catalysis. The related DEUBAD domain in INO80G inhibits UCH-L5 by exploiting similar structural elements in UCH-L5 to promote a radically different conformation, and employs molecular mimicry to block ubiquitin docking. In this process, large conformational changes create small but highly specific interfaces that mediate activity modulation of UCH-L5 by altering the affinity for substrates. Our results establish how related domains can exploit enzyme conformational plasticity to allosterically regulate DUB activity. These allosteric sites may present novel insights for pharmaceutical intervention in DUB activity.

Mechanism of UCH-L5 Activation and Inhibition by DEUBAD Domains in RPN13 and INO80G.,Sahtoe DD, van Dijk WJ, El Oualid F, Ekkebus R, Ovaa H, Sixma TK Mol Cell. 2015 Feb 17. pii: S1097-2765(14)01017-X. doi:, 10.1016/j.molcel.2014.12.039. PMID:25702870^[3]

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

References

↑ Yao T, Song L, Xu W, DeMartino GN, Florens L, Swanson SK, Washburn MP, Conaway RC, Conaway JW, Cohen RE. Proteasome recruitment and activation of the Uch37 deubiquitinating enzyme by Adrm1. Nat Cell Biol. 2006 Sep;8(9):994-1002. Epub 2006 Aug 13. PMID:16906146 doi:ncb1460
↑ Yao T, Song L, Jin J, Cai Y, Takahashi H, Swanson SK, Washburn MP, Florens L, Conaway RC, Cohen RE, Conaway JW. Distinct modes of regulation of the Uch37 deubiquitinating enzyme in the proteasome and in the Ino80 chromatin-remodeling complex. Mol Cell. 2008 Sep 26;31(6):909-17. doi: 10.1016/j.molcel.2008.08.027. PMID:18922472 doi:10.1016/j.molcel.2008.08.027
↑ Sahtoe DD, van Dijk WJ, El Oualid F, Ekkebus R, Ovaa H, Sixma TK. Mechanism of UCH-L5 Activation and Inhibition by DEUBAD Domains in RPN13 and INO80G. Mol Cell. 2015 Feb 17. pii: S1097-2765(14)01017-X. doi:, 10.1016/j.molcel.2014.12.039. PMID:25702870 doi:http://dx.doi.org/10.1016/j.molcel.2014.12.039

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/4uem"

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[4uem]] 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=4UEM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4UEM 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=4uem FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4uem OCA], [https://pdbe.org/4uem PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4uem RCSB], [https://www.ebi.ac.uk/pdbsum/4uem PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4uem 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]] 2.82&#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=4uem FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4uem OCA], [https://pdbe.org/4uem PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4uem RCSB], [https://www.ebi.ac.uk/pdbsum/4uem PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4uem ProSAT]</span></td></tr>
 </table>
 == Function ==

4uem

From Proteopedia

Current revision

UCH-L5 in complex with the RPN13 DEUBAD domain

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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