8ED9

cryo-EM structure of TRPM3 ion channel in the presence with PIP2 and PregS, state 2

8ED9 の概要

• エントリーDOI: 10.2210/pdb8ed9/pdb
• 関連するPDBエントリー: 8DDQ 8DDR 8DDS 8DDT 8DDU 8DDV 8DDW 8DDX 8ED7 8ED8
• EMDBエントリー: 28033
• 分子名称: Transient receptor potential cation channel, subfamily M, member 3, Unidentified segment at the N-terminus of TRPM3, 1,2-DIACYL-GLYCEROL-3-SN-PHOSPHATE, ... (6 entities in total)
• 機能のキーワード: trpm3, ion channel, pip2, membrane protein
• 由来する生物種: Mus musculus (house mouse); 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 632464.97

構造登録者

Zhao, C.,MacKinnon, R. (登録日: 2022-09-03, 公開日: 2022-11-09, 最終更新日: 2025-05-14)

主引用文献

Zhao, C.,MacKinnon, R.
Structural and functional analyses of a GPCR-inhibited ion channel TRPM3.
Neuron, 111:81-, 2023

PubMed Abstract: G-protein coupled receptors (GPCRs) govern the physiological response to stimuli by modulating the activity of downstream effectors, including ion channels. TRPM3 is an ion channel inhibited by GPCRs through direct interaction with G protein (Gβγ) released upon their activation. This GPCR-TRPM3 signaling pathway contributes to the analgesic effect of morphine. Here, we characterized Gβγ inhibition of TRPM3 using electrophysiology and single particle cryo-electron microscopy (cryo-EM). From electrophysiology, we obtained a half inhibition constant (IC50) of ∼240 nM. Using cryo-EM, we determined structures of mouse TRPM3 expressed in human cells with and without Gβγ and with and without PIP, a lipid required for TRPM3 activity, at resolutions of 2.7-4.7 Å. Gβγ-TRPM3 interfaces vary depending on PIP occupancy; however, in all cases, Gβγ appears loosely attached to TRPM3. The IC50 in electrophysiology experiments raises the possibility that additional unknown factors may stabilize the TRPM3-Gβγ complex.

PubMed: 36283409
DOI: 10.1016/j.neuron.2022.10.002

実験手法

ELECTRON MICROSCOPY (3.4 Å)