IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v6y2015i1d10.1038_ncomms8896.html
   My bibliography  Save this article

Chemically related 4,5-linked aminoglycoside antibiotics drive subunit rotation in opposite directions

Author

Listed:
  • Michael R. Wasserman

    (Weill Cornell Medical College)

  • Arto Pulk

    (University of California at Berkeley
    University of California at Berkeley)

  • Zhou Zhou

    (Weill Cornell Medical College)

  • Roger B. Altman

    (Weill Cornell Medical College)

  • John C. Zinder

    (Tri-Institutional Training Program in Chemical Biology, Weill Cornell Medical College, Rockefeller University, Memorial Sloan-Kettering Cancer Center)

  • Keith D. Green

    (University of Kentucky College of Pharmacy)

  • Sylvie Garneau-Tsodikova

    (University of Kentucky College of Pharmacy)

  • Jamie H. Doudna Cate

    (University of California at Berkeley
    University of California at Berkeley)

  • Scott C. Blanchard

    (Weill Cornell Medical College
    Tri-Institutional Training Program in Chemical Biology, Weill Cornell Medical College, Rockefeller University, Memorial Sloan-Kettering Cancer Center)

Abstract

Dynamic remodelling of intersubunit bridge B2, a conserved RNA domain of the bacterial ribosome connecting helices 44 (h44) and 69 (H69) of the small and large subunit, respectively, impacts translation by controlling intersubunit rotation. Here we show that aminoglycosides chemically related to neomycin—paromomycin, ribostamycin and neamine—each bind to sites within h44 and H69 to perturb bridge B2 and affect subunit rotation. Neomycin and paromomycin, which only differ by their ring-I 6′-polar group, drive subunit rotation in opposite directions. This suggests that their distinct actions hinge on the 6′-substituent and the drug’s net positive charge. By solving the crystal structure of the paromomycin–ribosome complex, we observe specific contacts between the apical tip of H69 and the 6′-hydroxyl on paromomycin from within the drug’s canonical h44-binding site. These results indicate that aminoglycoside actions must be framed in the context of bridge B2 and their regulation of subunit rotation.

Suggested Citation

  • Michael R. Wasserman & Arto Pulk & Zhou Zhou & Roger B. Altman & John C. Zinder & Keith D. Green & Sylvie Garneau-Tsodikova & Jamie H. Doudna Cate & Scott C. Blanchard, 2015. "Chemically related 4,5-linked aminoglycoside antibiotics drive subunit rotation in opposite directions," Nature Communications, Nature, vol. 6(1), pages 1-12, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8896
    DOI: 10.1038/ncomms8896
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms8896
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms8896?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. Dylan Girodat & Hans-Joachim Wieden & Scott C. Blanchard & Karissa Y. Sanbonmatsu, 2023. "Geometric alignment of aminoacyl-tRNA relative to catalytic centers of the ribosome underpins accurate mRNA decoding," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    2. Savannah M. Seely & Narayan P. Parajuli & Arindam Tarafder & Xueliang Ge & Suparna Sanyal & Matthieu G. Gagnon, 2023. "Molecular basis of the pleiotropic effects by the antibiotic amikacin on the ribosome," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    3. Narayan Prasad Parajuli & Andrew Emmerich & Chandra Sekhar Mandava & Michael Y. Pavlov & Suparna Sanyal, 2023. "Antibiotic thermorubin tethers ribosomal subunits and impedes A-site interactions to perturb protein synthesis in bacteria," Nature Communications, Nature, vol. 14(1), pages 1-14, 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:6:y:2015:i:1:d:10.1038_ncomms8896. 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.