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

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          Abstract

          Hsp90 is a ubiquitous molecular chaperone responsible for assembly and regulation of many eukaryotic signalling systems, and 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 inter-domain and inter-strand interactions, the detailed conformational changes in the N-terminal domain that accompany ATP binding, and the structural basis for stabilisation 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 is coupled to the chaperone ATPase cycle.

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          Author and article information

          Journal
          0410462
          6011
          Nature
          Nature
          Nature
          0028-0836
          1476-4687
          21 November 2017
          20 April 2006
          27 November 2017
          : 440
          : 7087
          : 1013-1017
          Affiliations
          [1 ]Section of Structural Biology, Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, U.K.
          [2 ]Pharmaceutical Science Research Division, King’s College London, Franklin-Wilkins Building, 150 Stamford Street, London SE1 9NN, U.K.
          [3 ]Department of Molecular Biology and Biotechnology, The University of Sheffield, Firth Court, Western Bank, Sheffield S10 2TN, UK
          Author notes
          Correspondence and requests for materials should be addressed to : LHP ( Laurence.Pearl@ 123456icr.ac.uk ).
          [§]

          Present address : Laboratoire d’Enzymologie et de Biochimie Structurales, CNRS, Avenue de la Terrasse, 91198 Gif sur Yvette, France

          Article
          PMC5703407 PMC5703407 5703407 ems75005
          10.1038/nature04716
          5703407
          16625188
          4e0a97d5-a33f-4eab-a21e-4d6a1f9a3979
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