Mechanics of Hsp70 chaperones enables differential interaction with client proteins

Nat Struct Mol Biol. 2011 Mar;18(3):345-51. doi: 10.1038/nsmb.2006. Epub 2011 Jan 30.

Abstract

Hsp70 chaperones interact with a wide spectrum of substrates ranging from unfolded to natively folded and aggregated proteins. Structural evidence suggests that bound substrates are entirely enclosed in a β-sheet cavity covered by a helical lid, which requires structural rearrangements including lid opening to allow substrate access. We analyzed the mechanics of the lid movement of bacterial DnaK by disulfide fixation of lid elements to the β-sheet and by electron paramagnetic resonance spectroscopy using spin labels in the lid and β-sheet. Our results indicate that the lid-forming helix B adopts at least three conformational states and, notably, does not close over bound proteins, implying that DnaK does not only bind to extended peptide stretches of protein substrates but can also accommodate regions with substantial tertiary structure. This flexible binding mechanism provides a basis for the broad spectrum of substrate conformers of Hsp70s.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allosteric Regulation
  • Disulfides / chemistry
  • Disulfides / metabolism
  • Escherichia coli / chemistry*
  • Escherichia coli / genetics
  • Escherichia coli / metabolism*
  • Escherichia coli Proteins / chemistry*
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism*
  • HSP70 Heat-Shock Proteins / chemistry*
  • HSP70 Heat-Shock Proteins / genetics
  • HSP70 Heat-Shock Proteins / metabolism*
  • Models, Molecular
  • Mutation
  • Protein Binding
  • Protein Structure, Secondary

Substances

  • Disulfides
  • Escherichia coli Proteins
  • HSP70 Heat-Shock Proteins
  • dnaK protein, E coli