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Elife. 2019 May 15;8. pii: e45779. doi: 10.7554/eLife.45779.

Symmetry transitions during gating of the TRPV2 ion channel in lipid membranes.

Author information

1
Department of Biochemistry, Duke University School of Medicine, Durham, United States.
2
Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, United States.

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.

KEYWORDS:

Ca2+ permeable channel; Oryctolagus cuniculus; TRP channel; cryo-EM; heat sensing ion channel; ligand gated ion channel; molecular biophysics; structural biology

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