Chaperoned ubiquitylation - Crystal structures of the CHIPU box E3 ubiquitin ligase and a CHIP-Ubc13-Uev1a complex
Zhang, M. H., Windheim, M., Roe, S. M., Peggie, M., Cohen, P., Prodromou, C., Pearl, L. H.
(2005)
Chaperoned ubiquitylation - Crystal structures of the CHIPU box E3 ubiquitin ligase and a CHIP-Ubc13-Uev1a complex.
MOLECULAR CELL, 20 (4).
pp. 525-538.
ISSN 1097-2765
Full text not available from this repository.
Abstract
Chaperoned ubiquitylation - Crystal structures of the CHIPU box E3 ubiquitin ligase and a CHIP-Ubc13-Uev1a complex CHIP is a dimeric U box E3 ubiquitin ligase that binds Hsp90 and/or Hsp70 via its TPR-domaln, 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-Uevla 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-ofsites activity, providing an elegant means for coupling a dimeric chaperone to a single ubiquitylation system.
Item Type: | Article |
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Authors (ICR Faculty only): | Pearl, Laurence and Prodromou, Chris |
All Authors: | Zhang, M. H., Windheim, M., Roe, S. M., Peggie, M., Cohen, P., Prodromou, C., Pearl, L. H. |
Uncontrolled Keywords: | Conjugating enzyme complex; nitric-oxide synthase; heat-shock proteins; polyubiquitin chain; dna-repair; degradation; identification; activation; pathway; kinase |
Research teams: | Closed research groups > Pearl Group |
Depositing User: | EPrints Services |
Date Deposited: | 10 Aug 2007 20:50 |
Last Modified: | 21 Apr 2015 09:34 |
URI: | http://publications.icr.ac.uk/id/eprint/2132 |
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