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Structural mechanism of heat-induced opening of a temperature-sensitive TRP channel

Published on 07.09.2021 in Nature Structural & Molecular Biology

Authors:

Kirill D. Nadezhdin, Arthur Neuberger, Yuri A. Trofimov, Nikolay A. Krylov, Viktor Sinica, Nikita Kupko, Viktorie Vlachova, Eleonora Zakharian, Roman G. Efremov & Alexander I. Sobolevsky

For the first time, temperature-induced ion channel opening is captured structurally!
For the first time, temperature-induced ion channel opening is captured structurally!

Numerous physiological functions rely on distinguishing temperature through temperature-sensitive transient receptor potential channels (thermo-TRPs). Although the function of thermo-TRPs has been studied extensively, structural determination of their heat- and cold-activated states has remained a challenge. Here, we present cryo-EM structures of the nanodisc-reconstituted wild-type mouse TRPV3 in three distinct conformations: closed, heat-activated sensitized and open states. The heat-induced transformations of TRPV3 are accompanied by changes in the secondary structure of the S2-S3 linker and the N and C termini and represent a conformational wave that links these parts of the protein to a lipid occupying the vanilloid binding site. State-dependent differences in the behavior of bound lipids suggest their active role in thermo-TRP temperature-dependent gating. Our structural data, supported by physiological recordings and molecular dynamics simulations, provide an insight for understanding the molecular mechanism of temperature sensing.

Our work was featured on NSMB July cover!

Cryo-EM structure of tetrameric integral membrane protein — TRPV3 with significant structural dynamics was resolved to a 1.98Å-resolution. Check the density quality below:

This work was done in collaboration with 3 different groups: Dr. Victorie Vlachova group from Institute of Physiology Czech Academy of Sciences, Prague, Czech Republic; Dr. Ella Zakharian group from University of Illinois College of Medicine, Peoria, IL, USA; and Dr. Roman G. Efremov group from Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.