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Co-translational folding of an alphavirus capsid protein in the cytosol of living cells

Nature Cell Biology volume 1, pages 341–345 (1999)Cite this article

Abstract

The Semliki Forest virus capsid protein contains a chymotrypsin-like protease domain that must fold before it can autocatalytically cleave the protein from a larger polyprotein precursor. Here we analyse this cleavage in living mammalian and prokaryotic cells, and find that it occurs immediately after the emergence of the protease domain from the ribosome during protein synthesis. The acquisition of the native conformation of this domain thus occurs rapidly and at the same time as translation. It does not require termination of translation or release from the ribosome, and nor does it involve Hsp70 binding. These results provide direct evidence that protein folding can occur co-translationally in the cytosol of both prokaryotes and eukaryotes.

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Figure 1: Co-translational folding and cleavage of C protein in living cells.
Figure 2: Effect of translation inhibitors on C-protein cleavage.
Figure 3: Association of Hsp70 with SFV structural proteins.
Figure 4: Folding of C-protein protease domain in the bacterial cytosol.

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Acknowledgements

We thank A. Mezzacasa and C. Schnatwinkel for assistance, and L. Ellgaard and M. Molinari for critically reading the manuscript. This work was supported by grants from the Swiss National Science Foundation and the Swiss Federal Institute of Technology-Zurich.

Correspondence and request for materials should be addressed to A.H.

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Authors and Affiliations

  1. Swiss Federal Institute of Technology, Institute of Biochemistry, Universitätstrasse 16, Zurich, CH-8092 , Switzerland

    Anthony V. Nicola & Ari Helenius

  2. Department of Cell Biology, Yale University School of Medicine, New Haven, 06250-8002 , Connecticut, USA

    Wei Chen

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  1. Anthony V. Nicola
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Correspondence to Ari Helenius.

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Nicola, A., Chen, W. & Helenius, A. Co-translational folding of an alphavirus capsid protein in the cytosol of living cells. Nat Cell Biol 1, 341–345 (1999). https://doi.org/10.1038/14032

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