Client-loading conformation of the Hsp90 molecular chaperone revealed in the cryo-EM structure of the human Hsp90:Hop complex

Mol Cell. 2011 Jun 24;42(6):771-81. doi: 10.1016/j.molcel.2011.04.023.


Hsp90 is an essential molecular chaperone required for the folding and activation of many hundreds of cellular "client" proteins. The ATP-dependent chaperone cycle involves significant conformational rearrangements of the Hsp90 dimer and interaction with a network of cochaperone proteins. Little is known about the mechanism of client protein binding or how cochaperone interactions modulate Hsp90 conformational states. We have determined the cryo-EM structure of the human Hsp90:Hop complex that receives client proteins from the Hsp70 chaperone. Hop stabilizes an alternate Hsp90 open state, where hydrophobic client-binding surfaces have converged and the N-terminal domains have rotated and match the closed, ATP conformation. Hsp90 is thus simultaneously poised for client loading by Hsp70 and subsequent N-terminal dimerization and ATP hydrolysis. Upon binding of a single Hsp70, the Hsp90:Hop conformation remains essentially unchanged. These results identify distinct functions for the Hop cochaperone, revealing an asymmetric mechanism for Hsp90 regulation and client loading.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate
  • Cryoelectron Microscopy*
  • Disulfides / chemistry
  • Disulfides / metabolism
  • HSP90 Heat-Shock Proteins / chemistry*
  • HSP90 Heat-Shock Proteins / ultrastructure
  • Homeodomain Proteins / chemistry*
  • Homeodomain Proteins / ultrastructure
  • Humans
  • Hydrolysis
  • Hydrophobic and Hydrophilic Interactions
  • Models, Molecular
  • Multiprotein Complexes / chemistry
  • Multiprotein Complexes / metabolism
  • Multiprotein Complexes / ultrastructure
  • Protein Conformation
  • Protein Multimerization
  • Surface Properties
  • Tumor Suppressor Proteins / chemistry*
  • Tumor Suppressor Proteins / ultrastructure


  • Disulfides
  • HOPX protein, human
  • HSP90 Heat-Shock Proteins
  • Homeodomain Proteins
  • Multiprotein Complexes
  • Tumor Suppressor Proteins
  • Adenosine Triphosphate