Journal
NATURE STRUCTURAL & MOLECULAR BIOLOGY
Volume 28, Issue 7, Pages 564-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41594-021-00615-4
Keywords
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Funding
- National Cancer Institute's National Cryo-EM Facility at the Frederick National Laboratory for Cancer Research [HSSN261200800001E]
- NIH [R01 CA206573, R01 NS083660, R01 NS107253, U24GM129547]
- Office of Biological and Environmental Research
- NIH Common Fund Transformative High Resolution Cryo-Electron Microscopy program [U24 GM129539]
- Simons Foundation [SF349247]
- NY State Assembly Majority
- Russian Science Foundation [18-14-00375]
- Russian Foundation for Basic Research [19-04-00350]
- Czech Science Foundation [19-03777S]
- NSF [1818086]
- Russian Science Foundation [21-14-28040] Funding Source: Russian Science Foundation
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Structural analysis of the TRPV3 channel at different temperatures reveals a conformational wave and the active role of lipids in temperature-dependent gating. These findings provide insights into the molecular mechanism of temperature sensing and have implications for understanding physiological functions regulated by thermosensitive TRP channels.
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. Cryo-EM structures of the heat-activated TRP channel TRPV3 in lipid nanodiscs at different temperatures reveal a conformational wave involved in the gating process.
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