1. Structural Biology and Molecular Biophysics
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Regulatory switch at the cytoplasmic interface controls TRPV channel gating

  1. Lejla Zubcevic
  2. William F Borschel
  3. Allen L Hsu
  4. Mario J Borgnia
  5. Seok-Yong Lee  Is a corresponding author
  1. Duke University School of Medicine, United States
  2. National Institute of Environmental Health Sciences, National Institutes of Health, United States
Research Article
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Cite this article as: eLife 2019;8:e47746 doi: 10.7554/eLife.47746

Abstract

Temperature-sensitive transient receptor potential vanilloid (thermoTRPV) channels are activated by ligands and heat, and are involved in various physiological processes. ThermoTRPV channels possess a large cytoplasmic ring consisting of N-terminal ankyrin repeat domains (ARD) and C-terminal domains (CTD). The cytoplasmic inter-protomer interface is unique and consists of a CTD coiled around a b-sheet which makes contacts with the neighboring ARD. Despite much existing evidence that the cytoplasmic ring is important for thermoTRPV function, the mechanism by which this unique structure is involved in thermoTRPV gating has not been clear. Here we present cryo-EM and electrophysiological studies which demonstrate that TRPV3 gating involves large rearrangements at the cytoplasmic inter-protomer interface and that this motion triggers coupling between cytoplasmic and transmembrane domains, priming the channel for opening. Furthermore, our studies unveil the role of this interface in the distinct biophysical and physiological properties of individual thermoTRPV subtypes.

Article and author information

Author details

  1. Lejla Zubcevic

    Department of Biochemistry, Duke University School of Medicine, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1884-9235
  2. William F Borschel

    Department of Biochemistry, Duke University School of Medicine, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Allen L Hsu

    Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2065-3802
  4. Mario J Borgnia

    Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Seok-Yong Lee

    Department of Biochemistry, Duke University School of Medicine, Durham, United States
    For correspondence
    seok-yong.lee@duke.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0662-9921

Funding

National Institute of Neurological Disorders and Stroke (R35NS097241)

  • Seok-Yong Lee

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Kenton Jon Swartz, National Institute of Neurological Disorders and Stroke, National Institutes of Health, United States

Publication history

  1. Received: April 16, 2019
  2. Accepted: May 8, 2019
  3. Accepted Manuscript published: May 9, 2019 (version 1)

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

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