How Do Chaperones Protect a Cell's Proteins from Oxidative Damage?

Cell Syst. 2018 Jun 27;6(6):743-751.e3. doi: 10.1016/j.cels.2018.05.001. Epub 2018 Jun 6.


The accumulation of protein damage in aging organisms is thought to contribute to many aging-related diseases. Yet the properties determining which proteins are most susceptible remain poorly understood. Are certain conformations more vulnerable? Which chaperones are the main guardians? We address these questions with a system-wide model of E. coli proteostasis. By predicting how proteins with different folding properties respond to each chaperone's concentration, the model computes "damage fingerprints" that identify unfolded conformations as the major damage target. What matters most is not a protein's stability or difficulty of folding, but its dwell time in an unfolded state. The main guardian chaperone is DnaK because its client proteins spend more time unfolded than clients of GroEL, providing a mechanism for why the cell's capacity to handle stress is more sensitive to DnaK levels. Also, we find that chaperones are protectors, not recyclers. This model describes how cells resist stress and indicates that designing chaperone-targeting drugs may require whole-cell, system-wide modeling.

Keywords: DnaK; E. coli; GroEL; HSP70; chaperone; protein damage; protein folding; protein oxidation; proteostasis; stationary phase.

Publication types

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

MeSH terms

  • Bacterial Proteins / metabolism
  • Chaperonin 60 / metabolism
  • Escherichia coli / metabolism
  • Escherichia coli Proteins / metabolism
  • HSP70 Heat-Shock Proteins / metabolism
  • Heat-Shock Proteins / metabolism
  • Molecular Chaperones / metabolism
  • Molecular Chaperones / physiology*
  • Oxidative Stress / physiology*
  • Protective Agents / metabolism
  • Protein Folding
  • Protein Unfolding
  • Proteostasis / physiology*
  • Staphylococcal Protein A / metabolism


  • Bacterial Proteins
  • Chaperonin 60
  • Escherichia coli Proteins
  • HSP70 Heat-Shock Proteins
  • Heat-Shock Proteins
  • Molecular Chaperones
  • Protective Agents
  • Staphylococcal Protein A
  • dnaK protein, E coli