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

Ali, Maruf M U, Roe, S Mark, Vaughan, Cara K, Meyer, Phillipe, Panaretou, Barry, Piper, Peter W, Prodromou, Chrisostomos and Pearl, Laurence H (2006) Crystal structure of an Hsp90-nucleotide-p23/Sba1 closed chaperone complex. Nature, 440. pp. 1013-1017. ISSN 0028-0836

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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.

Item Type: Article
Schools and Departments: School of Life Sciences > Biochemistry
Depositing User: Mark Roe
Date Deposited: 06 Feb 2012 18:53
Last Modified: 25 Feb 2015 06:53
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