Structural highlights
Function
[TRPV3_MOUSE] Putative receptor-activated non-selective calcium permeant cation channel. It is activated by innocuous (warm) temperatures and shows an increased response at noxious temperatures greater than 39 degrees Celsius. Activation exhibits an outward rectification. May associate with TRPV1 and may modulate its activity. Is a negative regulator of hair growth and cycling: TRPV3-coupled signaling suppresses keratinocyte proliferation in hair follicles and induces apoptosis and premature hair follicle regression (catagen) (By similarity).
Publication Abstract from PubMed
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.
Structural mechanism of heat-induced opening of a temperature-sensitive TRP channel.,Nadezhdin KD, Neuberger A, Trofimov YA, Krylov NA, Sinica V, Kupko N, Vlachova V, Zakharian E, Efremov RG, Sobolevsky AI Nat Struct Mol Biol. 2021 Jul;28(7):564-572. doi: 10.1038/s41594-021-00615-4., Epub 2021 Jul 8. PMID:34239124[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Nadezhdin KD, Neuberger A, Trofimov YA, Krylov NA, Sinica V, Kupko N, Vlachova V, Zakharian E, Efremov RG, Sobolevsky AI. Structural mechanism of heat-induced opening of a temperature-sensitive TRP channel. Nat Struct Mol Biol. 2021 Jul;28(7):564-572. doi: 10.1038/s41594-021-00615-4., Epub 2021 Jul 8. PMID:34239124 doi:http://dx.doi.org/10.1038/s41594-021-00615-4
