1. Biochemistry and Chemical Biology
  2. Structural Biology and Molecular Biophysics
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The shape of the ribosome exit tunnel affects cotranslational protein folding

  1. Renuka Kudva
  2. Pengfei Tian
  3. Fátima Pardo-Avila
  4. Marta Carroni
  5. Robert Best
  6. Harris D Bernstein
  7. Gunnar von Heijne  Is a corresponding author
  1. Stockholm University, Sweden
  2. National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, United States
  3. Stanford University, United States
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Cite this article as: eLife 2018;7:e36326 doi: 10.7554/eLife.36326

Abstract

The E.coli ribosome exit tunnel can accommodate small folded proteins, while larger ones fold outside. It remains unclear, however, to what extent the geometry of the tunnel influences protein folding. Here, using E. coli ribosomes with deletions in loops in proteins uL23 and uL24 that protrude into the tunnel, we investigate how tunnel geometry determines where proteins of different sizes fold. We find that a 29-residue zinc-finger domain normally folding close to the uL23 loop folds deeper in the tunnel in uL23 Dloop ribosomes, while two ~100-residue protein normally folding close to the uL24 loop near the tunnel exit port fold at deeper locations in uL24 Dloop ribosomes, in good agreement with results obtained by coarse-grained molecular dynamics simulations. This supports the idea that cotranslational folding commences once a protein domain reaches a location in the exit tunnel where there is sufficient space to house the folded structure.

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Author details

  1. Renuka Kudva

    Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0426-3716
  2. Pengfei Tian

    Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Fátima Pardo-Avila

    Department of Structural Biology, Stanford University, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Marta Carroni

    Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7697-6427
  5. Robert Best

    Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7893-3543
  6. Harris D Bernstein

    Genetics and Biochemistry Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4941-3741
  7. Gunnar von Heijne

    Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden
    For correspondence
    gunnar@dbb.su.se
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4490-8569

Funding

Knut och Alice Wallenbergs Stiftelse (2012.0282)

  • Gunnar von Heijne

Vetenskapsrådet (621-2014-3713)

  • Gunnar von Heijne

Cancerfonden (15 0888)

  • Gunnar von Heijne

National Institutes of Health (Intramural)

  • Robert Best

National Institutes of Health (Intramural)

  • Harris D Bernstein

National Institutes of Health (R35GM122543)

  • Fátima Pardo-Avila

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. John Kuriyan, University of California, Berkeley, United States

Publication history

  1. Received: March 1, 2018
  2. Accepted: November 26, 2018
  3. Accepted Manuscript published: November 26, 2018 (version 1)

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

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