Letter | Published:

Trigger factor in complex with the ribosome forms a molecular cradle for nascent proteins

Nature volume 431, pages 590596 (30 September 2004) | Download Citation

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Abstract

During protein biosynthesis, nascent polypeptide chains that emerge from the ribosomal exit tunnel encounter ribosome-associated chaperones, which assist their folding to the native state1,2. Here we present a 2.7 Å crystal structure of Escherichia coli trigger factor, the best-characterized chaperone of this type, together with the structure of its ribosome-binding domain in complex with the Haloarcula marismortui large ribosomal subunit. Trigger factor adopts a unique conformation resembling a crouching dragon with separated domains forming the amino-terminal ribosome-binding ‘tail’, the peptidyl-prolyl isomerase ‘head’, the carboxy-terminal ‘arms’ and connecting regions building up the ‘back’. From its attachment point on the ribosome, trigger factor projects the extended domains over the exit of the ribosomal tunnel, creating a protected folding space where nascent polypeptides may be shielded from proteases and aggregation. This study sheds new light on our understanding of co-translational protein folding, and suggests an unexpected mechanism of action for ribosome-associated chaperones.

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Acknowledgements

Data collection was performed at the Swiss Light Source, Paul Scherrer Institut, Villigen and at the Swiss Norwegian Beamline (ESRF, Grenoble). We are grateful to C. Schulze-Briese, T. Tomizaki and A. Wagner at the SLS as well as P. Pattison and S. Capelli at the SNBL whose outstanding efforts have made these experiments possible. We also thank our colleagues S. Antolic, M. Steiner and members of the Ban laboratory for help in ribosome preparations and suggestions; and members of the Bukau laboratory for discussions. This work was supported by the Swiss National Science Foundation (SNSF), the NCCR Structural Biology program of the SNSF, an ETH research grant, grants of the Deutsche Forschungsgemeinschaft to B.B. and E.D. and a Young Investigator grant from the Human Frontier Science Program to N.B. and E.D.

Author information

Affiliations

  1. Institut für Molekularbiologie und Biophysik, Eidgenössische Technische Hochschule Hönggerberg (ETH Zürich), HPK Gebäude, CH-8093 Zürich, Switzerland

    • Lars Ferbitz
    • , Timm Maier
    •  & Nenad Ban
  2. Zentrum für Molekulare Biologie (ZMBH), Universität Heidelberg, Im Neuenheimer Feld 282, D-69120 Heidelberg, Germany

    • Holger Patzelt
    • , Bernd Bukau
    •  & Elke Deuerling

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Competing interests

The authors declare that they have no competing financial interests.

Corresponding authors

Correspondence to Elke Deuerling or Nenad Ban.

Supplementary information

Image files

  1. 1.

    Supplementary Figure 1

    Example of experimental electron density quality.

  2. 2.

    Supplementary Figure 2

    Structural flexibility of the Trigger Factor.

  3. 3.

    Supplementary Figure 3

    Crystal contact sites of the full-length Trigger Factor.

  4. 4.

    Supplementary Figure 4

    E.coli Trigger Factor associates with Haloarcula marismortui 50S and crosslinks to the ribosomal protein L23.

  5. 5.

    Supplementary Figure 5

    Sequence conservation of L23 and ribosomal RNA at the TF binding site.

Word documents

  1. 1.

    Supplementary Table

    Data collection and refinement statistics.

  2. 2.

    Supplementary Figure Legends and methods used for figure preparation

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DOI

https://doi.org/10.1038/nature02899

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