Trigger factor and DnaK cooperate in folding of newly synthesized proteins

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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 proteins1 and the Hsp70 homologue DnaK is not essential for protein folding or cell viability at intermediate growth temperatures2. The major protein associated with nascent polypeptides is ribosome-bound trigger factor3,4, which displays chaperone and prolyl isomerase activities in vitro3,5,6. Here we show that Δtig::kan mutants lacking trigger factor have no defects in growth or protein folding. However, combined Δtig::kan and ΔdnaK mutations cause synthetic lethality. Depletion of DnaK in the Δtig::kan mutant results in massive aggregation of cytosolic proteins. In Δtig::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.