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Structural mechanism of heat-induced opening of a temperature-sensitive TRP channel
KD. Nadezhdin, A. Neuberger, YA. Trofimov, NA. Krylov, V. Sinica, N. Kupko, V. Vlachova, E. Zakharian, RG. Efremov, AI. Sobolevsky
Language English Country United States
Document type Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.
Grant support
R01 NS107253
NINDS NIH HHS - United States
U24 GM129539
NIGMS NIH HHS - United States
R01 NS083660
NINDS NIH HHS - United States
U24 GM129547
NIGMS NIH HHS - United States
R01 CA206573
NCI NIH HHS - United States
NLK
ProQuest Central
from 2004-01-01 to 1 year ago
Health & Medicine (ProQuest)
from 2004-01-01 to 1 year ago
- MeSH
- Cell Line MeSH
- Cryoelectron Microscopy MeSH
- Ion Channel Gating MeSH
- HEK293 Cells MeSH
- TRPV Cation Channels metabolism MeSH
- Protein Conformation MeSH
- Humans MeSH
- Lipids chemistry MeSH
- Mice MeSH
- Cold Temperature MeSH
- Thermodynamics MeSH
- Protein Binding physiology MeSH
- Thermosensing physiology MeSH
- Hot Temperature MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, N.I.H., Extramural MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
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.
Department of Biochemistry and Molecular Biophysics Columbia University New York NY USA
National Research Nuclear University Moscow Engineering Physics Institute Moscow Russia
National Research University Higher School of Economics Moscow Russia
Shemyakin Ovchinnikov Institute of Bioorganic Chemistry Russian Academy of Sciences Moscow Russia
References provided by Crossref.org
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