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 PubMedTransient receptor potential vanilloid subfamily member 3 (TRPV3) is a temperature-sensitive cation channel. Previous cryo-EM analyses of TRPV3 in detergent micelles or amphipol proposed that the lower gate opens by alpha-to-pi helical transitions of the nearby S6 helix. However, it remains unclear how physiological lipids are involved in the TRPV3 activation. Here we determined the apo state structure of mouse (Mus musculus) TRPV3 in a lipid nanodisc at 3.3 A resolution. The structure revealed that lipids bound to the pore domain stabilize the selectivity filter in the narrow state, suggesting that the selectivity filter of TRPV3 affects cation permeation. When the lower gate is closed in nanodisc-reconstituted TRPV3, the S6 helix adopts the pi-helical conformation without agonist- or heat-sensitization, potentially stabilized by putative intra-subunit hydrogen bonds and lipid binding. Our findings provide insights into the lipid-associated gating mechanism of TRPV3. The structure of lipid nanodisc-reconstituted TRPV3 reveals the gating mechanism.,Shimada H, Kusakizako T, Dung Nguyen TH, Nishizawa T, Hino T, Tominaga M, Nureki O Nat Struct Mol Biol. 2020 Jun 22. pii: 10.1038/s41594-020-0439-z. doi:, 10.1038/s41594-020-0439-z. PMID:32572254[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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