Ali, M.M.U., Roe, S.M., Vaughan, C.K. et al. (5 more authors) (2006) Crystal structure of an Hsp90-nucleotide-p23/Sba1 closed chaperone complex. Nature, 440 (7087). pp. 1013-1017. ISSN 0028-0836
Abstract
Hsp90 (heat shock protein of 90 kDa) is a ubiquitous molecular chaperone responsible for the assembly and regulation of many eukaryotic signalling systems and is an emerging target for rational chemotherapy of many cancers. Although the structures of isolated domains of Hsp90 have been determined, the arrangement and ATP-dependent dynamics of these in the full Hsp90 dimer have been elusive and contentious. Here we present the crystal structure of full-length yeast Hsp90 in complex with an ATP analogue and the co-chaperone p23/Sba1. The structure reveals the complex architecture of the ‘closed’ state of the Hsp90 chaperone, the extensive interactions between domains and between protein chains, the detailed conformational changes in the amino-terminal domain that accompany ATP binding, and the structural basis for stabilization of the closed state by p23/Sba1. Contrary to expectations, the closed Hsp90 would not enclose its client proteins but provides a bipartite binding surface whose formation and disruption are coupled to the chaperone ATPase cycle.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2006 Nature Publishing Group. This is an author produced version of a paper subsequently published in Nature. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | HSP90 MOLECULAR CHAPERONE; N-TERMINAL DOMAIN; ESCHERICHIA-COLI HSP90; SHOCK-PROTEIN 90; ATPASE ACTIVITY; CLIENT PROTEIN; STEROID-RECEPTOR; BINDING SITE; IN-VIVO; P23 |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) > Department of Molecular Biology and Biotechnology (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 22 Dec 2017 09:44 |
Last Modified: | 26 Dec 2017 18:38 |
Published Version: | https://doi.org/10.1038/nature04716 |
Status: | Published |
Publisher: | Nature Publishing Group |
Refereed: | Yes |
Identification Number: | 10.1038/nature04716 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:124688 |