6co4
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Structure of the Rpn13-Rpn2 complex provides insights for Rpn13 and Uch37 as anticancer targets== | |
| + | <StructureSection load='6co4' size='340' side='right'caption='[[6co4]]' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6co4]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=2nbk 2nbk]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CO4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6CO4 FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=6co4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6co4 OCA], [https://pdbe.org/6co4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6co4 RCSB], [https://www.ebi.ac.uk/pdbsum/6co4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6co4 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/ADRM1_HUMAN ADRM1_HUMAN] Functions as a proteasomal ubiquitin receptor. Recruits the deubiquitinating enzyme UCHL5 at the 26S proteasome and promotes its activity.<ref>PMID:16990800</ref> <ref>PMID:17139257</ref> <ref>PMID:16815440</ref> <ref>PMID:16906146</ref> <ref>PMID:18497817</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Proteasome-ubiquitin receptor hRpn13/Adrm1 binds and activates deubiquitinating enzyme Uch37/UCHL5 and is targeted by bis-benzylidine piperidone RA190, which restricts cancer growth in mice xenografts. Here, we solve the structure of hRpn13 with a segment of hRpn2 that serves as its proteasome docking site; a proline-rich C-terminal hRpn2 extension stretches across a narrow canyon of the ubiquitin-binding hRpn13 Pru domain blocking an RA190-binding surface. Biophysical analyses in combination with cell-based assays indicate that hRpn13 binds preferentially to hRpn2 and proteasomes over RA190. hRpn13 also exists outside of proteasomes where it may be RA190 sensitive. RA190 does not affect hRpn13 interaction with Uch37, but rather directly binds and inactivates Uch37. hRpn13 deletion from HCT116 cells abrogates RA190-induced accumulation of substrates at proteasomes. We propose that RA190 targets hRpn13 and Uch37 through parallel mechanisms and at proteasomes, RA190-inactivated Uch37 cannot disassemble hRpn13-bound ubiquitin chains. | ||
| - | + | Structure of the Rpn13-Rpn2 complex provides insights for Rpn13 and Uch37 as anticancer targets.,Lu X, Nowicka U, Sridharan V, Liu F, Randles L, Hymel D, Dyba M, Tarasov SG, Tarasova NI, Zhao XZ, Hamazaki J, Murata S, Burke TR Jr, Walters KJ Nat Commun. 2017 Jun 9;8:15540. doi: 10.1038/ncomms15540. PMID:28598414<ref>PMID:28598414</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: Lu | + | <div class="pdbe-citations 6co4" style="background-color:#fffaf0;"></div> |
| - | [[Category: Walters | + | == References == |
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Lu X]] | ||
| + | [[Category: Walters KJ]] | ||
Current revision
Structure of the Rpn13-Rpn2 complex provides insights for Rpn13 and Uch37 as anticancer targets
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