IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v7y2016i1d10.1038_ncomms12026.html
   My bibliography  Save this article

A combined cryo-EM and molecular dynamics approach reveals the mechanism of ErmBL-mediated translation arrest

Author

Listed:
  • Stefan Arenz

    (University of Munich)

  • Lars V. Bock

    (Max Planck Institute for Biophysical Chemistry)

  • Michael Graf

    (University of Munich)

  • C. Axel Innis

    (Institut Européen de Chimie et Biologie, University of Bordeaux
    INSERM U1212
    CNRS UMR7377)

  • Roland Beckmann

    (University of Munich
    Center for integrated Protein Science Munich, University of Munich)

  • Helmut Grubmüller

    (Max Planck Institute for Biophysical Chemistry)

  • Andrea C. Vaiana

    (Max Planck Institute for Biophysical Chemistry)

  • Daniel N. Wilson

    (University of Munich
    Center for integrated Protein Science Munich, University of Munich)

Abstract

Nascent polypeptides can induce ribosome stalling, regulating downstream genes. Stalling of ErmBL peptide translation in the presence of the macrolide antibiotic erythromycin leads to resistance in Streptococcus sanguis. To reveal this stalling mechanism we obtained 3.6-Å-resolution cryo-EM structures of ErmBL-stalled ribosomes with erythromycin. The nascent peptide adopts an unusual conformation with the C-terminal Asp10 side chain in a previously unseen rotated position. Together with molecular dynamics simulations, the structures indicate that peptide-bond formation is inhibited by displacement of the peptidyl-tRNA A76 ribose from its canonical position, and by non-productive interactions of the A-tRNA Lys11 side chain with the A-site crevice. These two effects combine to perturb peptide-bond formation by increasing the distance between the attacking Lys11 amine and the Asp10 carbonyl carbon. The interplay between drug, peptide and ribosome uncovered here also provides insight into the fundamental mechanism of peptide-bond formation.

Suggested Citation

  • Stefan Arenz & Lars V. Bock & Michael Graf & C. Axel Innis & Roland Beckmann & Helmut Grubmüller & Andrea C. Vaiana & Daniel N. Wilson, 2016. "A combined cryo-EM and molecular dynamics approach reveals the mechanism of ErmBL-mediated translation arrest," Nature Communications, Nature, vol. 7(1), pages 1-14, November.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12026
    DOI: 10.1038/ncomms12026
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms12026
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms12026?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Corentin R. Fostier & Farès Ousalem & Elodie C. Leroy & Saravuth Ngo & Heddy Soufari & C. Axel Innis & Yaser Hashem & Grégory Boël, 2023. "Regulation of the macrolide resistance ABC-F translation factor MsrD," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    2. Martino Morici & Sara Gabrielli & Keigo Fujiwara & Helge Paternoga & Bertrand Beckert & Lars V. Bock & Shinobu Chiba & Daniel N. Wilson, 2024. "RAPP-containing arrest peptides induce translational stalling by short circuiting the ribosomal peptidyltransferase activity," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    3. Sakshi Jain & Lukasz Koziej & Panagiotis Poulis & Igor Kaczmarczyk & Monika Gaik & Michal Rawski & Namit Ranjan & Sebastian Glatt & Marina V. Rodnina, 2023. "Modulation of translational decoding by m6A modification of mRNA," Nature Communications, Nature, vol. 14(1), pages 1-13, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12026. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.