title: Trigger factor and DnaK cooperate in folding of newly synthesized proteins.
abstract: 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.
authors.affiliation: Institut für Biochemie und Molekularbiologie, Freiburg, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Deuerling
authors.forename: A
authors.initials: A
authors.lastname: Schulze-Specking
authors.forename: T
authors.initials: T
authors.lastname: Tomoyasu
authors.forename: A
authors.initials: A
authors.lastname: Mogk
authors.forename: B
authors.initials: B
authors.lastname: Bukau
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000378:metabolism / Q000502:physiology*; D018834:Chaperonin 60 / Q000378:metabolism; D004351:Drug Resistance / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism*; D029968:Escherichia coli Proteins; D018840:HSP70 Heat-Shock Proteins / Q000502:physiology*; D007612:Kanamycin / Q000494:pharmacology; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D019696:Peptidylprolyl Isomerase / Q000502:physiology*; D017510:Protein Folding
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D018834:Chaperonin 60; D029968:Escherichia coli Proteins; D018840:HSP70 Heat-Shock Proteins; D007612:Kanamycin; D008156:Luciferases; C063842:dnaK protein, E coli; D019696:Peptidylprolyl Isomerase