1. Structural Biology and Molecular Biophysics
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Symmetry transitions during gating of the TRPV2 ion channel in lipid membranes

  1. Lejla Zubcevic
  2. Allen L Hsu
  3. Mario J Borgnia
  4. 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:e45779 doi: 10.7554/eLife.45779

Abstract

The Transient Receptor Potential Vanilloid 2 (TRPV2) channel is a member of the temperature-sensing thermoTRPV family. Recent advances in cryo-electronmicroscopy (cryo-EM) and X-ray crystallography have provided many important insights into the gating mechanisms of thermoTRPV channels. Interestingly, crystallographic studies of ligand-dependent TRPV2 gating have shown that the TRPV2 channel adopts two-fold symmetric arrangements during the gating cycle. However, it was unclear if crystal packing forces played a role in stabilizing the two-fold symmetric arrangement of the channel. Here we employ cryo-EM to elucidate the structure of full-length rabbit TRPV2 in complex with the agonist resiniferatoxin (RTx) in nanodiscs and amphipol. We show that RTx induces two-fold symmetric conformations of TRPV2 in both environments. However, the two-fold symmetry is more pronounced in the native-like lipid environment of the nanodiscs. Our data offers insights into a gating pathway in TRPV2 involving symmetry transitions.

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. 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
  3. 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.
  4. 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

National Institute of Environmental Health Sciences (ZIC ES103326)

  • Meario J Borgnia

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: February 4, 2019
  2. Accepted: May 14, 2019
  3. Accepted Manuscript published: May 15, 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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