7X6C

Cryo-EM structure of the human TRPC5 ion channel in lipid nanodiscs, class1

7X6C の概要

• エントリーDOI: 10.2210/pdb7x6c/pdb
• EMDBエントリー: 33021
• 分子名称: Short transient receptor potential channel 5, PHOSPHATIDYLETHANOLAMINE, (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate, ... (7 entities in total)
• 機能のキーワード: trp, transient receptor potential, metal transport
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 370532.67

構造登録者

Won, J.,Jeong, H.,Lee, H.H. (登録日: 2022-03-07, 公開日: 2023-05-24, 最終更新日: 2024-10-23)

主引用文献

Won, J.,Kim, J.,Jeong, H.,Kim, J.,Feng, S.,Jeong, B.,Kwak, M.,Ko, J.,Im, W.,So, I.,Lee, H.H.
Molecular architecture of the G alpha i -bound TRPC5 ion channel.
Nat Commun, 14:2550-2550, 2023

PubMed Abstract: G-protein coupled receptors (GPCRs) and ion channels serve as key molecular switches through which extracellular stimuli are transformed into intracellular effects, and it has long been postulated that ion channels are direct effector molecules of the alpha subunit of G-proteins (Gα). However, no complete structural evidence supporting the direct interaction between Gα and ion channels is available. Here, we present the cryo-electron microscopy structures of the human transient receptor potential canonical 5 (TRPC5)-Gα complexes with a 4:4 stoichiometry in lipid nanodiscs. Remarkably, Gα binds to the ankyrin repeat edge of TRPC5 ~ 50 Å away from the cell membrane. Electrophysiological analysis shows that Gα increases the sensitivity of TRPC5 to phosphatidylinositol 4,5-bisphosphate (PIP), thereby rendering TRPC5 more easily opened in the cell membrane, where the concentration of PIP is physiologically regulated. Our results demonstrate that ion channels are one of the direct effector molecules of Gα proteins triggered by GPCR activation-providing a structural framework for unraveling the crosstalk between two major classes of transmembrane proteins: GPCRs and ion channels.

PubMed: 37137991
DOI: 10.1038/s41467-023-38281-3

実験手法

ELECTRON MICROSCOPY (3.15 Å)