Trigger factor and DnaK cooperate in folding of newly synthesized proteins

Nature. 1999 Aug 12;400(6745):693-6. doi: 10.1038/23301.


The role of molecular chaperones in assisting the folding of newly synthesized proteins in the cytosol is poorly understood. In Escherichia coli, GroEL assists folding of only a minority of proteins and the Hsp70 homologue DnaK is not essential for protein folding or cell viability at intermediate growth temperatures. The major protein associated with nascent polypeptides is ribosome-bound trigger factor, which displays chaperone and prolyl isomerase activities in vitro. Here we show that delta tig::kan mutants lacking trigger factor have no defects in growth or protein folding. However, combined delta tig::kan and delta dnaK mutations cause synthetic lethality. Depletion of DnaK in the delta tig::kan mutant results in massive aggregation of cytosolic proteins. In delta tig::kan cells, an increased amount of newly synthesized proteins associated transiently with DnaK. These findings show in vivo activity for a ribosome-associated chaperone, trigger factor, in general protein folding, and functional cooperation of this protein with a cytosolic Hsp70. Trigger factor and DnaK cooperate to promote proper folding of a variety of E. coli proteins, but neither is essential for folding and viability at intermediate growth temperatures.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Bacterial Proteins / metabolism
  • Bacterial Proteins / physiology*
  • Chaperonin 60 / metabolism
  • Drug Resistance / genetics
  • Escherichia coli / genetics
  • Escherichia coli / metabolism*
  • Escherichia coli Proteins*
  • HSP70 Heat-Shock Proteins / physiology*
  • Kanamycin / pharmacology
  • Luciferases / genetics
  • Luciferases / metabolism
  • Mutation
  • Peptidylprolyl Isomerase / physiology*
  • Protein Folding*


  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Chaperonin 60
  • Escherichia coli Proteins
  • HSP70 Heat-Shock Proteins
  • Kanamycin
  • Luciferases
  • dnaK protein, E coli
  • Peptidylprolyl Isomerase