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

温度感受性陽イオンチャネルTRPV3をナノディスク内に再構成し、より生体に近い形で構造を明らかにした。
TRPV3は温度感知や血圧調節に重要な役割を担っている。このチャネルの開閉メカニズムを詳細に解明するため、細胞表面に存在する状態に近い形で作製し、熱により脂質が解離することでチャネルが開閉する温度感受の機構を明らかにした。

Abstract

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.

分解能

3.3 Å（膜貫通ドメインは約2.9 Å）

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