IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v5y2014i1d10.1038_ncomms4501.html
   My bibliography  Save this article

Molecular basis for erythromycin-dependent ribosome stalling during translation of the ErmBL leader peptide

Author

Listed:
  • Stefan Arenz

    (Gene Center, University of Munich)

  • Haripriya Ramu

    (Center for Pharmaceutical Biotechnology, University of Illinois)

  • Pulkit Gupta

    (Center for Pharmaceutical Biotechnology, University of Illinois)

  • Otto Berninghausen

    (Gene Center, University of Munich)

  • Roland Beckmann

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

  • Nora Vázquez-Laslop

    (Center for Pharmaceutical Biotechnology, University of Illinois)

  • Alexander S. Mankin

    (Center for Pharmaceutical Biotechnology, University of Illinois)

  • Daniel N. Wilson

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

Abstract

In bacteria, ribosome stalling during translation of ErmBL leader peptide occurs in the presence of the antibiotic erythromycin and leads to induction of expression of the downstream macrolide resistance methyltransferase ErmB. The lack of structures of drug-dependent stalled ribosome complexes (SRCs) has limited our mechanistic understanding of this regulatory process. Here we present a cryo-electron microscopy structure of the erythromycin-dependent ErmBL-SRC. The structure reveals that the antibiotic does not interact directly with ErmBL, but rather redirects the path of the peptide within the tunnel. Furthermore, we identify a key peptide–ribosome interaction that defines an important relay pathway from the ribosomal tunnel to the peptidyltransferase centre (PTC). The PTC of the ErmBL-SRC appears to adopt an uninduced state that prevents accommodation of Lys-tRNA at the A-site, thus providing structural basis for understanding how the drug and the nascent peptide cooperate to inhibit peptide bond formation and induce translation arrest.

Suggested Citation

  • Stefan Arenz & Haripriya Ramu & Pulkit Gupta & Otto Berninghausen & Roland Beckmann & Nora Vázquez-Laslop & Alexander S. Mankin & Daniel N. Wilson, 2014. "Molecular basis for erythromycin-dependent ribosome stalling during translation of the ErmBL leader peptide," Nature Communications, Nature, vol. 5(1), pages 1-8, May.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4501
    DOI: 10.1038/ncomms4501
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms4501
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms4501?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.

    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:5:y:2014:i:1:d:10.1038_ncomms4501. 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.