| Chaperoned ubiquitylation--crystal structures of the CHIP U box E3 ubiquitin ligase and a CHIP-Ubc13-Uev1a complex. | |
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MedLine Citation:
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PMID: 16307917 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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CHIP is a dimeric U box E3 ubiquitin ligase that binds Hsp90 and/or Hsp70 via its TPR-domain, facilitating ubiquitylation of chaperone bound client proteins. We have determined the crystal structure of CHIP bound to an Hsp90 C-terminal decapeptide. The structure explains how CHIP associates with either chaperone type and reveals an unusual asymmetric homodimer in which the protomers adopt radically different conformations. Additionally, we identified CHIP as a functional partner of Ubc13-Uev1a in formation of Lys63-linked polyubiquitin chains, extending CHIP's roles into ubiquitin regulation as well as targeted destruction. The structure of Ubc13-Uev1a bound to the CHIP U box domain defines the basis for selective cooperation of CHIP with specific ubiquitin-conjugating enzymes. Remarkably, the asymmetric arrangement of the TPR domains in the CHIP dimer occludes one Ubc binding site, so that CHIP operates with half-of-sites activity, providing an elegant means for coupling a dimeric chaperone to a single ubiquitylation system. |
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Authors:
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Minghao Zhang; Mark Windheim; S Mark Roe; Mark Peggie; Philip Cohen; Chrisostomos Prodromou; Laurence H Pearl |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Molecular cell Volume: 20 ISSN: 1097-2765 ISO Abbreviation: Mol. Cell Publication Date: 2005 Nov |
Date Detail:
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Created Date: 2005-11-25 Completed Date: 2006-01-05 Revised Date: 2007-08-13 |
Medline Journal Info:
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Nlm Unique ID: 9802571 Medline TA: Mol Cell Country: United States |
Other Details:
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Languages: eng Pagination: 525-38 Citation Subset: IM |
Affiliation:
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Section of Structural Biology, Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, United Kingdom. |
| Data Bank Information | |
Bank Name/Acc. No.:
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PDB/2C2L; 2C2V |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Line Crystallography, X-Ray Dimerization HSP90 Heat-Shock Proteins / metabolism Humans Lysine / metabolism Mice Polyubiquitin / metabolism Protein Structure, Tertiary Transcription Factors / chemistry*, metabolism Ubiquitin-Conjugating Enzymes / chemistry*, metabolism Ubiquitin-Protein Ligases / chemistry*, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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//Wellcome Trust |
| Chemical | |
Reg. No./Substance:
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0/HSP90 Heat-Shock Proteins; 0/Transcription Factors; 120904-94-1/Polyubiquitin; 56-87-1/Lysine; EC 6.3.2.19/CHIP protein, mouse; EC 6.3.2.19/STUB1 protein, human; EC 6.3.2.19/UBE2N protein, human; EC 6.3.2.19/UBE2V1 protein, human; EC 6.3.2.19/Ubiquitin-Conjugating Enzymes; EC 6.3.2.19/Ubiquitin-Protein Ligases |
| Comments/Corrections | |
Comment In:
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Mol Cell. 2005 Dec 9;20(5):653-5
[PMID:
16337587
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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