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TitleStructural mechanism of heat-induced opening of a temperature-sensitive TRP channel.
Journal, issue, pagesNat Struct Mol Biol, Vol. 28, Issue 7, Page 564-572, Year 2021
Publish dateJul 8, 2021
AuthorsKirill D Nadezhdin / Arthur Neuberger / Yuri A Trofimov / Nikolay A Krylov / Viktor Sinica / Nikita Kupko / Viktorie Vlachova / Eleonora Zakharian / Roman G Efremov / Alexander I Sobolevsky /
PubMed AbstractNumerous physiological functions rely on distinguishing temperature through temperature-sensitive transient receptor potential channels (thermo-TRPs). Although the function of thermo-TRPs has been ...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.
External linksNat Struct Mol Biol / PubMed:34239124 / PubMed Central
MethodsEM (single particle)
Resolution1.98 - 3.86 Å
Structure data

EMDB-23853, PDB-7mij:
Mouse TRPV3 in MSP2N2 nanodiscs, closed state at 4 degrees Celsius
Method: EM (single particle) / Resolution: 1.98 Å

EMDB-23854, PDB-7mik:
Mouse TRPV3 in MSP2N2 nanodiscs, closed state at 42 degrees Celsius
Method: EM (single particle) / Resolution: 3.12 Å

EMDB-23855, PDB-7mil:
Mouse TRPV3 in MSP2N2 nanodiscs, sensitized state at 42 degrees Celsius
Method: EM (single particle) / Resolution: 3.86 Å

EMDB-23856, PDB-7mim:
Mouse TRPV3 in cNW11 nanodiscs, closed state at 4 degrees Celsius
Method: EM (single particle) / Resolution: 3.42 Å

EMDB-23857, PDB-7min:
Mouse TRPV3 in cNW11 nanodiscs, closed state at 42 degrees Celsius
Method: EM (single particle) / Resolution: 3.09 Å

EMDB-23858, PDB-7mio:
Mouse TRPV3 in cNW11 nanodiscs, open state at 42 degrees Celsius
Method: EM (single particle) / Resolution: 3.48 Å

Chemicals

ChemComp-POV:
(2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate / phospholipid*YM

ChemComp-NA:
Unknown entry

ChemComp-HOH:
WATER

Source
  • mus musculus (house mouse)
KeywordsMEMBRANE PROTEIN / Transient Receptor Potential V Family Member 3 / TRP channel / TRPV3 / closed state at 4 degrees Celsius / MSP2N2 / closed state at 42 degrees Celsius / sensitized state at 42 degrees Celsius / cNW11 / open state at 42 degrees Celsius

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