IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v7y2016i1d10.1038_ncomms11734.html
   My bibliography  Save this article

Identification of an activation site in Bak and mitochondrial Bax triggered by antibodies

Author

Listed:
  • Sweta Iyer

    (The Walter and Eliza Hall Institute of Medical Research)

  • Khatira Anwari

    (The Walter and Eliza Hall Institute of Medical Research)

  • Amber E. Alsop

    (The Walter and Eliza Hall Institute of Medical Research)

  • Wai Shan Yuen

    (Development and Stem Cells Program, Monash University, Melbourne)

  • David C. S. Huang

    (The Walter and Eliza Hall Institute of Medical Research)

  • John Carroll

    (Development and Stem Cells Program, Monash University, Melbourne)

  • Nicholas A. Smith

    (La Trobe Institute for Molecular Sciences, La Trobe University)

  • Brian J. Smith

    (La Trobe Institute for Molecular Sciences, La Trobe University)

  • Grant Dewson

    (The Walter and Eliza Hall Institute of Medical Research)

  • Ruth M. Kluck

    (The Walter and Eliza Hall Institute of Medical Research)

Abstract

During apoptosis, Bak and Bax are activated by BH3-only proteins binding to the α2–α5 hydrophobic groove; Bax is also activated via a rear pocket. Here we report that antibodies can directly activate Bak and mitochondrial Bax by binding to the α1–α2 loop. A monoclonal antibody (clone 7D10) binds close to α1 in non-activated Bak to induce conformational change, oligomerization, and cytochrome c release. Anti-FLAG antibodies also activate Bak containing a FLAG epitope close to α1. An antibody (clone 3C10) to the Bax α1–α2 loop activates mitochondrial Bax, but blocks translocation of cytosolic Bax. Tethers within Bak show that 7D10 binding directly extricates α1; a structural model of the 7D10 Fab bound to Bak reveals the formation of a cavity under α1. Our identification of the α1–α2 loop as an activation site in Bak paves the way to develop intrabodies or small molecules that directly and selectively regulate these proteins.

Suggested Citation

  • Sweta Iyer & Khatira Anwari & Amber E. Alsop & Wai Shan Yuen & David C. S. Huang & John Carroll & Nicholas A. Smith & Brian J. Smith & Grant Dewson & Ruth M. Kluck, 2016. "Identification of an activation site in Bak and mitochondrial Bax triggered by antibodies," Nature Communications, Nature, vol. 7(1), pages 1-10, September.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11734
    DOI: 10.1038/ncomms11734
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms11734
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms11734?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
    ---><---

    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_ncomms11734. 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.