Severe oxidative stress causes inactivation of DnaK and activation of the redox-regulated chaperone Hsp33

Mol Cell. 2005 Feb 4;17(3):381-92. doi: 10.1016/j.molcel.2004.12.027.


DnaK/DnaJ/GrpE constitutes the primary chaperone machinery in E. coli that functions to protect proteins against heat-induced protein aggregation. Surprisingly, upon exposure of cells to reactive oxygen species at elevated temperature, proteins are no longer protected by the DnaK system. Instead, they bind now to the redox-regulated chaperone Hsp33, which is activated by the same conditions that inactivate DnaK. The inactivation of DnaK seems to be induced by the dramatic decrease in intracellular ATP levels that occurs upon exposure of cells to reactive oxygen species. This appears to render DnaK's N-terminal ATPase domain nucleotide depleted and thermolabile. DnaK's N terminus reversibly unfolds in vivo, and DnaK loses its ability to protect proteins against stress-induced aggregation. Now, the ATP-independent chaperone holdase Hsp33 binds to a large number of cellular proteins and prevents their irreversible aggregation. Upon return to nonstress conditions, Hsp33 becomes inactivated while DnaK reactivates and resumes its task to support protein folding.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Cysteine / chemistry
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Escherichia coli Proteins / antagonists & inhibitors
  • Escherichia coli Proteins / chemistry
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism*
  • HSP70 Heat-Shock Proteins / antagonists & inhibitors
  • HSP70 Heat-Shock Proteins / chemistry
  • HSP70 Heat-Shock Proteins / genetics
  • HSP70 Heat-Shock Proteins / metabolism*
  • Heat-Shock Proteins / genetics
  • Heat-Shock Proteins / metabolism*
  • Heat-Shock Response
  • Kinetics
  • Models, Biological
  • Molecular Chaperones / genetics
  • Molecular Chaperones / metabolism*
  • Oxidation-Reduction
  • Oxidative Stress
  • Protein Denaturation
  • Protein Structure, Tertiary
  • Reactive Oxygen Species / metabolism


  • Escherichia coli Proteins
  • HSP33 protein, E coli
  • HSP70 Heat-Shock Proteins
  • Heat-Shock Proteins
  • Molecular Chaperones
  • Reactive Oxygen Species
  • Adenosine Triphosphate
  • dnaK protein, E coli
  • Cysteine