The structure of lipid nanodisc-reconstituted TRPV3 reveals the gating mechanism

Transient 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 α-to-π helical transitions of the nearby S6 helix. However, it remains unclear how p...

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Vydané v:Nature structural & molecular biology Ročník 27; číslo 7; s. 645 - 652
Hlavní autori: Shimada, Hiroto, Kusakizako, Tsukasa, Dung Nguyen, T H, Nishizawa, Tomohiro, Hino, Tomoya, Tominaga, Makoto, Nureki, Osamu
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: United States Nature Publishing Group 01.07.2020
Predmet:
Cations
Channel gating
Conformation
Cryoelectron Microscopy
Domains
Hydrogen Bonding
Hydrogen bonds
Ion Channel Gating - physiology
Ion channels
Ions
Lipids
Lipids - chemistry
Micelles
Models, Molecular
Nanostructures - chemistry
Protein Conformation
Selectivity
Transient receptor potential proteins
TRPV Cation Channels - chemistry
TRPV Cation Channels - metabolism
ISSN:1545-9993, 1545-9985, 1545-9985
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Popis
Shrnutí:Transient 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 α-to-π 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 Å 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 π-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.
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ISSN:1545-9993
1545-9985
1545-9985
DOI:10.1038/s41594-020-0439-z