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Trigger factor and DnaK cooperate in folding of newly synthesized proteins

Nature volume 400, pages 693–696 (1999)Cite this article

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.

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Figure 1: Synthetic lethality.
Figure 2: Specific activity and aggregation of firefly luciferase.
Figure 3: Aggregation of pre-existing and newly synthesized E. coli proteins.
Figure 4: Association of DnaK with nascent polypeptide chains.

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Acknowledgements

We thank members of the Bukau lab, T. Hesterkamp, M. Müller and H.-G. Koch for comments on the manuscript and discussions. This work was supported by grants of the DFG and the Fonds der Chemie to B.B.

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  1. Institut für Biochemie und Molekularbiologie, Hermann-Herder-Strasse 7, 79104, D-Freiburg, Germany

    Elke Deuerling, Agnes Schulze-Specking, Toshifumi Tomoyasu, Axel Mogk & Bernd Bukau

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  1. Elke Deuerling
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Correspondence to Bernd Bukau.

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Deuerling, E., Schulze-Specking, A., Tomoyasu, T. et al. Trigger factor and DnaK cooperate in folding of newly synthesized proteins. Nature 400, 693–696 (1999). https://doi.org/10.1038/23301

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