EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	Structural basis for agonist and heat activation of nociceptor TRPM3.
ジャーナル・号・ページ	Nat Struct Mol Biol, Year 2025
掲載日	2025年10月24日
著者	Sushant Kumar / Fei Jin / Sung Jin Park / Wooyoung Choi / Sarah I Keuning / Richard P Massimino / Simon Vu / Wei Lü / Juan Du /
PubMed 要旨	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 ...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.
リンク	Nat Struct Mol Biol / PubMed:41136608
手法	EM (単粒子)
解像度	2.62 - 6.74 Å
構造データ	48811 9n1g EMDB-48811, PDB-9n1g: Cryo-EM structure of rabbit TRPM3 in apo resting state at 18 degrees Celsius 手法: EM (単粒子) / 解像度: 2.62 Å 48812 9n1h EMDB-48812, PDB-9n1h: Cryo-EM structure of rabbit TRPM3 in apo resting state at 37 degrees Celsius 手法: EM (単粒子) / 解像度: 3.23 Å 48813 9n1i EMDB-48813, PDB-9n1i: Cryo-EM structure of rabbit TRPM3 in complex with CIM0216 in resting state at 18 degrees Celsius 手法: EM (単粒子) / 解像度: 6.74 Å 48814 9n1j EMDB-48814, PDB-9n1j: Cryo-EM structure of rabbit TRPM3 in apo activated state at 18 degrees Celsius 手法: EM (単粒子) / 解像度: 3.91 Å 48815 9n1k EMDB-48815, PDB-9n1k: Cryo-EM structure of rabbit TRPM3 in apo activated state at 37 degrees Celsius 手法: EM (単粒子) / 解像度: 3.68 Å 48816 9n1l EMDB-48816, PDB-9n1l: Cryo-EM structure of rabbit TRPM3 in complex with primidone in resting state at 18 degrees Celsius 手法: EM (単粒子) / 解像度: 2.93 Å 48817 9n1m EMDB-48817, PDB-9n1m: Cryo-EM structure of rabbit TRPM3 in complex with primidone in activated state at 18 degrees Celsius 手法: EM (単粒子) / 解像度: 2.93 Å 48819 9n1n EMDB-48819, PDB-9n1n: Cryo-EM structure of rabbit TRPM3 in complex with CIM0216 in activated state at 18 degrees Celsius 手法: EM (単粒子) / 解像度: 3.2 Å 48877 9n4j EMDB-48877, PDB-9n4j: Cryo-EM structure of rabbit TRPM3 in complex with CIM0216 at 18 degrees Celsius 手法: EM (単粒子) / 解像度: 3.27 Å 70209 9o7w EMDB-70209, PDB-9o7w: Cryo-EM structure of apo rabbit TRPM3 having 3 resting and 1 activated subunits at 18 degrees Celsius 手法: EM (単粒子) / 解像度: 3.2 Å 70210 9o7x EMDB-70210, PDB-9o7x: Cryo-EM structure of apo rabbit TRPM3 having 2 resting and 2 activated subunits (ortho position) at 18 degrees Celsius 手法: EM (単粒子) / 解像度: 3.17 Å 70211 9o7y EMDB-70211, PDB-9o7y: Cryo-EM structure of apo rabbit TRPM3 having 2 resting and 2 activated subunits (para position) at 18 degrees Celsius 手法: EM (単粒子) / 解像度: 3.48 Å 70212 9o7z EMDB-70212, PDB-9o7z: Cryo-EM structure of apo rabbit TRPM3 having 1 resting and 3 activated subunits at 18 degrees Celsius 手法: EM (単粒子) / 解像度: 3.6 Å 70213 9o80 EMDB-70213, PDB-9o80: Cryo-EM structure of apo rabbit TRPM3 having 3 resting and 1 activated subunits at 37 degrees Celsius 手法: EM (単粒子) / 解像度: 3.77 Å 70214 9o81 EMDB-70214, PDB-9o81: Cryo-EM structure of apo rabbit TRPM3 having 2 resting and 2 activated subunits (ortho position) at 37 degrees Celsius 手法: EM (単粒子) / 解像度: 3.96 Å 70215 9o82 EMDB-70215, PDB-9o82: Cryo-EM structure of apo rabbit TRPM3 having 2 resting and 2 activated subunits (para position) at 37 degrees Celsius 手法: EM (単粒子) / 解像度: 4.46 Å 70216 9o83 EMDB-70216, PDB-9o83: Cryo-EM structure of apo rabbit TRPM3 having 1 resting and 3 activated subunits at 37 degrees Celsius 手法: EM (単粒子) / 解像度: 3.96 Å 70218 9o86 EMDB-70218, PDB-9o86: Cryo-EM structure of CIM0216-bound rabbit TRPM3 having 3 resting and 1 activated subunits at 18 degrees Celsius 手法: EM (単粒子) / 解像度: 4.11 Å 70219 9o87 EMDB-70219, PDB-9o87: Cryo-EM structure of CIM0216-bound rabbit TRPM3 having 2 resting and 2 activated subunits (ortho position) at 18 degrees Celsius 手法: EM (単粒子) / 解像度: 3.77 Å 70220 9o88 EMDB-70220, PDB-9o88: Cryo-EM structure of CIM0216-bound rabbit TRPM3 having 2 resting and 2 activated subunits (para position) at 18 degrees Celsius 手法: EM (単粒子) / 解像度: 3.96 Å 70221 9o89 EMDB-70221, PDB-9o89: Cryo-EM structure of CIM0216-bound rabbit TRPM3 having 1 resting and 3 activated subunits at 18 degrees Celsius 手法: EM (単粒子) / 解像度: 3.41 Å 70222 9o8c EMDB-70222, PDB-9o8c: Cryo-EM structure of primidone-bound rabbit TRPM3 having 3 resting and 1 activated subunits at 18 degrees Celsius 手法: EM (単粒子) / 解像度: 3.2 Å 70225 9o8f EMDB-70225, PDB-9o8f: Cryo-EM structure of primidone-bound rabbit TRPM3 having 2 resting and 2 activated subunits (para position) at 18 degrees Celsius 手法: EM (単粒子) / 解像度: 3.91 Å 70226 9o8g EMDB-70226, PDB-9o8g: Cryo-EM structure of primidone-bound rabbit TRPM3 having 1 resting and 3 activated subunits at 18 degrees Celsius 手法: EM (単粒子) / 解像度: 3.48 Å
化合物	ChemComp-Y01: CHOLESTEROL HEMISUCCINATE PDB-1aib: STRUCTURAL BASIS FOR THE CATALYTIC ACTIVITY OF ASPARTATE AMINOTRANSFERASE K258H LACKING THE PYRIDOXAL-5'-PHOSPHATE BINDING LYSINE RESIDUE PDB-1aia: STRUCTURAL BASIS FOR THE CATALYTIC ACTIVITY OF ASPARTATE AMINOTRANSFERASE K258H LACKING THE PYRIDOXAL-5'-PHOSPHATE BINDING LYSINE RESIDUE
由来	oryctolagus cuniculus (ウサギ)
キーワード	MEMBRANE PROTEIN / TRPM3 / ion channel