Publication: Structural mechanism of heat-induced opening of a temperature-sensitive TRP channel
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2021
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© 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.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.
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Structural mechanism of heat-induced opening of a temperature-sensitive TRP channel / Nadezhdin, K.D. [et al.] // Nature Structural and Molecular Biology. - 2021. - 10.1038/s41594-021-00615-4
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https://www.doi.org/10.1038/s41594-021-00615-4
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https://openrepository.mephi.ru/handle/123456789/24386
https://www.scopus.com/record/display.uri?eid=2-s2.0-85109966115&origin=resultslist
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=Alerting&SrcApp=Alerting&DestApp=WOS_CPL&DestLinkType=FullRecord&UT=WOS:000670865500003
https://openrepository.mephi.ru/handle/123456789/24386