IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v12y2021i1d10.1038_s41467-020-20788-8.html
   My bibliography  Save this article

Mechanism of pore opening in the calcium-activated chloride channel TMEM16A

Author

Listed:
  • Andy K. M. Lam

    (Department of Biochemistry, University of Zurich)

  • Raimund Dutzler

    (Department of Biochemistry, University of Zurich)

Abstract

The anion channel TMEM16A is activated by intracellular Ca2+ in a highly cooperative process. By combining electrophysiology and autocorrelation analysis, we investigated the mechanism of channel activation and the concurrent rearrangement of the gate in the narrow part of the pore. Features in the fluctuation characteristics of steady-state current indicate the sampling of intermediate conformations that are successively occupied during gating. The initial step is related to conformational changes induced by Ca2+ binding, which is ensued by rearrangements that open the pore. Mutations in the gate shift the equilibrium of transitions in a manner consistent with a progressive destabilization of this region during pore opening. We come up with a mechanism of channel activation where the binding of Ca2+ induces conformational changes in the protein that, in a sequential manner, propagate from the binding site and couple to the gate in the narrow pore to allow ion permeation.

Suggested Citation

  • Andy K. M. Lam & Raimund Dutzler, 2021. "Mechanism of pore opening in the calcium-activated chloride channel TMEM16A," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-020-20788-8
    DOI: 10.1038/s41467-020-20788-8
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-020-20788-8
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-020-20788-8?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. Melanie Arndt & Carolina Alvadia & Monique S. Straub & Vanessa Clerico Mosina & Cristina Paulino & Raimund Dutzler, 2022. "Structural basis for the activation of the lipid scramblase TMEM16F," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    2. Andy K. M. Lam & Sonja Rutz & Raimund Dutzler, 2022. "Inhibition mechanism of the chloride channel TMEM16A by the pore blocker 1PBC," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    3. Zhongjie Ye & Nicola Galvanetto & Leonardo Puppulin & Simone Pifferi & Holger Flechsig & Melanie Arndt & Cesar Adolfo Sánchez Triviño & Michael Palma & Shifeng Guo & Horst Vogel & Anna Menini & Clemen, 2024. "Structural heterogeneity of the ion and lipid channel TMEM16F," Nature Communications, Nature, vol. 15(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:12:y:2021:i:1:d:10.1038_s41467-020-20788-8. 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.