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

• Published in: eLife 2019-05, Vol.8
• Main Authors: Zubcevic, Lejla, Hsu, Allen L, Borgnia, Mario J, Lee, Seok-Yong
• Format: Article
• Language: English
• Subjects: Animals; Binding sites; Ca2+ permeable channel; Channel gating; Classification; cryo-EM; Cryoelectron Microscopy; Crystallography; Data collection; Datasets; Diterpenes - metabolism; heat sensing ion channel; Ion channels; ligand gated ion channel; Lipid membranes; Membranes - enzymology; Oryctolagus cuniculus; Physiological aspects; Physiology; Protein Binding; Protein Conformation; Rabbits; Resiniferatoxin; Structural Biology and Molecular Biophysics; Symmetry; Transient receptor potential proteins; TRP channel; TRPV Cation Channels - metabolism; TRPV Cation Channels - ultrastructure; X-ray crystallography
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.45779

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.