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Crystal structure of an Hsp90-nucleotide-p23/Sba1 closed chaperone complex

journal contribution
posted on 2023-06-07, 21:41 authored by Maruf M U Ali, S Mark Roe, Cara K Vaughan, Phillipe Meyer, Barry Panaretou, Peter W Piper, Chrisostomos ProdromouChrisostomos Prodromou, Laurence PearlLaurence Pearl
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.

History

Publication status

  • Published

Journal

Nature

ISSN

0028-0836

Publisher

Nature Publishing Group

Volume

440

Page range

1013-1017

Department affiliated with

  • Biochemistry Publications

Full text available

  • No

Peer reviewed?

  • Yes

Legacy Posted Date

2012-02-06

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