9O86

Cryo-EM structure of CIM0216-bound rabbit TRPM3 having 3 resting and 1 activated subunits at 18 degrees Celsius

これはPDB形式変換不可エントリーです。

9O86 の概要

• エントリーDOI: 10.2210/pdb9o86/pdb
• EMDBエントリー: 70218
• 分子名称: TRPM3, (2S)-2-(3,4-dihydroquinolin-1(2H)-yl)-N-(5-methyl-1,2-oxazol-3-yl)-2-phenylacetamide (2 entities in total)
• 機能のキーワード: trpm3, ion channel, membrane protein
• 由来する生物種: Oryctolagus cuniculus
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 604750.95

構造登録者

Kumar, S.,Lu, W.,Du, J. (登録日: 2025-04-15, 公開日: 2025-12-17, 最終更新日: 2026-02-04)

主引用文献

Kumar, S.,Jin, F.,Park, S.J.,Choi, W.,Keuning, S.I.,Massimino, R.P.,Vu, S.,Lu, W.,Du, J.
Structural basis for agonist and heat activation of nociceptor TRPM3.
Nat.Struct.Mol.Biol., 33:34-42, 2026

PubMed Abstract: Detecting noxious heat is vital for survival, triggering protective pain responses. The TRPM3 channel is a key nociceptor and a promising therapeutic target for pain and neurological disorders. Here we show that the rabbit TRPM3 is intrinsically dynamic, with its intracellular domain (ICD) sampling both resting and activated states, but favoring the resting state in the absence of stimulation. We reveal that heat and the synthetic agonist CIM0216 shift the equilibrium toward activation by inducing a similar ICD rearrangement. Mutations that facilitate ICD movement enhance sensitivity to both thermal and chemical stimuli, underscoring the central role of the ICD in channel gating. We also show that the antagonist primidone binds the same site as CIM0216 in the S1-S4 domain but inhibits channel activation. This study provides a structural framework for a mechanistic understanding of thermal and chemical gating of TRPM3 and for guiding the rational design of TRPM3-targeted analgesics and neurotherapeutics.

PubMed: 41136608
DOI: 10.1038/s41594-025-01692-5

実験手法

ELECTRON MICROSCOPY (4.11 Å)