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The ribosome as a platform for co-translational processing, folding and targeting of newly synthesized proteins

Nature Structural & Molecular Biology volume 16, pages 589–597 (2009)Cite this article

Abstract

The early events in the life of newly synthesized proteins in the cellular environment are remarkably complex. Concurrently with their synthesis by the ribosome, nascent polypeptides are subjected to enzymatic processing, chaperone-assisted folding or targeting to translocation pores at membranes. The ribosome itself has a key role in these different tasks and governs the interplay between the various factors involved. Indeed, the ribosome serves as a platform for the spatially and temporally regulated association of enzymes, targeting factors and chaperones that act upon the nascent polypeptides emerging from the exit tunnel. Furthermore, the ribosome provides opportunities to coordinate the protein-synthesis activity of its peptidyl transferase center with the protein targeting and folding processes. Here we review the early co-translational events involving the ribosome that guide cytosolic proteins to their native state.

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Figure 1: The path of the nascent chain through the ribosomal exit tunnel.
Figure 2: N-terminal co-translational enzymatic processing and modification of nascent polypeptides in the vicinity of the ribosome.
Figure 3: Model of bacterial chaperones involved in de novo protein folding.
Figure 4: Interaction of Trigger factor with nascent chains.
Figure 5: Model of eukaryotic chaperones presumably involved in de novo protein folding.
Figure 6: Spatial arrangement of nascent chain–processing factors around the tunnel exit (star).

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Acknowledgements

We thank members of the Bukau and Ban laboratories for critical reading of the manuscript. We acknowledge the help of Y. Cully, F. Gloge and A. Rutkowska in preparing parts of the figures. Work in the authors' laboratories is supported by grants from the Deutsche Forschungsgemeinschaft (DFG) to B.B. and G.K. (SFB 638, FOR967), the Swiss National Science Foundation (SNSF), the National Center of Excellence in Research (NCCR) Structural Biology programme of the SNSF and the ETH Research Grant TH-3/04-1 to N.B., and the Federation of European Biochemical Societies long-term fellowship to D.B.

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  1. Zentrum für Molekulare Biologie der Universität Heidelberg, DKFZ-ZMBH Allianz, Heidelberg, Germany

    Günter Kramer & Bernd Bukau

  2. Institut für Molekularbiologie und Biophysik, ETH Zürich, Zürich, Switzerland

    Daniel Boehringer & Nenad Ban

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  1. Günter Kramer
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Correspondence to Bernd Bukau.

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Kramer, G., Boehringer, D., Ban, N. et al. The ribosome as a platform for co-translational processing, folding and targeting of newly synthesized proteins. Nat Struct Mol Biol 16, 589–597 (2009). https://doi.org/10.1038/nsmb.1614

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