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

0544567 - FGÚ 2022 RIV US eng J - Článek v odborném periodiku
Nadezhdin, K. D. - Neuberger, A. - Trofimov, Yu. A. - Krylov, N. A. - Sinica, Viktor - Kupko, N. - Vlachová, Viktorie - Zakharian, E. - Efremov, R. G. - Sobolevsky, A. I.
Structural mechanism of heat-induced opening of a temperature-sensitive TRP channel.
Nature Structural & Molecular Biology. Roč. 28, č. 7 (2021), s. 564-572. ISSN 1545-9993. E-ISSN 1545-9985
Grant CEP: GA ČR(CZ) GA19-03777S
Institucionální podpora: RVO:67985823
Klíčová slova: temperature sensitive TRP channel * gating * heat-activated channel * structure-function * vanilloid TRP channel
Obor OECD: Neurosciences (including psychophysiology
Impakt faktor: 18.361, rok: 2021
Způsob publikování: Omezený přístup
https://doi.org/10.1038/s41594-021-00615-4

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.
Trvalý link: http://hdl.handle.net/11104/0321415