Symmetry transitions during gating of the TRPV2 ion channel in lipid membranes
- Duke University School of Medicine, United States
- National Institute of Environmental Health Sciences, National Institutes of Health, United States
- Cited 8
- Views 1,399
- Annotations
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
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
- Kenton Jon Swartz, National Institute of Neurological Disorders and Stroke, National Institutes of Health, United States
Publication history
- Received: February 4, 2019
- Accepted: May 14, 2019
- Accepted Manuscript published: May 15, 2019 (version 1)
- Version of Record published: May 31, 2019 (version 2)
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.
Metrics
-
- 1,399
- Page views
-
- 321
- Downloads
-
- 8
- Citations
Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.
Download links
Downloads (link to download the article as PDF)
Download citations (links to download the citations from this article in formats compatible with various reference manager tools)
Open citations (links to open the citations from this article in various online reference manager services)
Further reading
-
- Structural Biology and Molecular Biophysics
-
- Cell Biology
- Structural Biology and Molecular Biophysics
