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	Mechanisms of sensory adaptation and inhibition of the cold and menthol receptor TRPM8.
ジャーナル・号・ページ	Sci Adv, Vol. 10, Issue 31, Page eadp2211, Year 2024
掲載日	2024年8月2日
著者	Ying Yin / Cheon-Gyu Park / Feng Zhang / Justin G Fedor / Shasha Feng / Yang Suo / Wonpil Im / Seok-Yong Lee /
PubMed 要旨	Our sensory adaptation to cold and chemically induced coolness is mediated by the intrinsic property of TRPM8 channels to desensitize. TRPM8 is also implicated in cold-evoked pain disorders and ...Our sensory adaptation to cold and chemically induced coolness is mediated by the intrinsic property of TRPM8 channels to desensitize. TRPM8 is also implicated in cold-evoked pain disorders and migraine, highlighting its inhibitors as an avenue for pain relief. Despite the importance, the mechanisms of TRPM8 desensitization and inhibition remained unclear. We found, using cryo-electron microscopy, electrophysiology, and molecular dynamics simulations, that TRPM8 inhibitors bind selectively to the desensitized state of the channel. These inhibitors were used to reveal the overlapping mechanisms of desensitization and inhibition and that cold and cooling agonists share a common desensitization pathway. Furthermore, we identified the structural determinants crucial for the conformational change in TRPM8 desensitization. Our study illustrates how receptor-level conformational changes alter cold sensation, providing insights into therapeutic development.
リンク	Sci Adv / PubMed:39093967 / PubMed Central
手法	EM (単粒子)
解像度	2.76 - 4.13 Å
構造データ	44255 9b6d EMDB-44255, PDB-9b6d: Cryo-EM structure of the mouse TRPM8 channel in the ligand-free desensitized state 手法: EM (単粒子) / 解像度: 3.3 Å 44256 9b6e EMDB-44256, PDB-9b6e: Cryo-EM structure of the mouse TRPM8 channel in complex with the antagonist TC-I 2014 手法: EM (単粒子) / 解像度: 2.91 Å 44257 9b6f EMDB-44257, PDB-9b6f: Cryo-EM structure of the mouse TRPM8 channel in complex with the antagonist AMG2850 手法: EM (単粒子) / 解像度: 3.42 Å 44258 9b6g EMDB-44258, PDB-9b6g: Cryo-EM structure of the mouse TRPM8 channel in complex with the antagonist AMTB 手法: EM (単粒子) / 解像度: 2.81 Å 44259 9b6h EMDB-44259, PDB-9b6h: Cryo-EM structure of the mouse TRPM8 channel in complex with the antagonist TC-I 2014 and the cooling agonist C3 手法: EM (単粒子) / 解像度: 2.76 Å 44260 9b6i EMDB-44260, PDB-9b6i: Cryo-EM structure of the avian great tit TRPM8 channel in complex with the antagonist TC-I 2014 手法: EM (単粒子) / 解像度: 3.26 Å 44261 9b6j EMDB-44261, PDB-9b6j: Cryo-EM structure of the mouse TRPM8 channel in complex with PI(4,5)P2 and Ca2+ 手法: EM (単粒子) / 解像度: 3.53 Å 44262 9b6k EMDB-44262, PDB-9b6k: Cryo-EM structure of the mouse TRPM8 channel in complex with Ca2+ in the absence of PI(4,5)P2 手法: EM (単粒子) / 解像度: 4.13 Å
化合物	ChemComp-Y01: CHOLESTEROL HEMISUCCINATE ChemComp-T14: 3-{7-(trifluoromethyl)-5-[2-(trifluoromethyl)phenyl]-1H-benzimidazol-2-yl}-1-oxa-2-azaspiro[4.5]dec-2-ene PDB-1aiy: R6 HUMAN INSULIN HEXAMER (SYMMETRIC), NMR, 10 STRUCTURES ChemComp-LQ7: N-(3-aminopropyl)-2-[(3-methylphenyl)methoxy]-N-[(thiophen-2-yl)methyl]benzamide ChemComp-NAG: 2-acetamido-2-deoxy-beta-D-glucopyranose ChemComp-ULO: nonyl(oxo)di(propan-2-yl)-lambda~5~-phosphane ChemComp-CA: Unknown entry ChemComp-PIO: [(2R)-2-octanoyloxy-3-[oxidanyl-[(1R,2R,3S,4R,5R,6S)-2,3,6-tris(oxidanyl)-4,5-diphosphonooxy-cyclohexyl]oxy-phosphoryl]oxy-propyl] octanoate
由来	mus musculus (ハツカネズミ) parus major (シジュウカラ)
キーワード	MEMBRANE PROTEIN / TRPM8 / menthol receptor / cold receptor / PI(4 / 5)P2 / cooling agonists / temperature sensing / ion channel / sensory transduction / transient receptor potential ion channel / TRPM8 activation / TRPM8 inhibition / TRPM8 desensitization / TRPM8 antagonists