Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Mechanisms of sensory adaptation and inhibition of the cold and menthol receptor TRPM8.
Journal, issue, pages	Sci Adv, Vol. 10, Issue 31, Page eadp2211, Year 2024
Publish date	Aug 2, 2024
Authors	Ying Yin / Cheon-Gyu Park / Feng Zhang / Justin G Fedor / Shasha Feng / Yang Suo / Wonpil Im / Seok-Yong Lee /
PubMed Abstract	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.
External links	Sci Adv / PubMed:39093967 / PubMed Central
Methods	EM (single particle)
Resolution	2.76 - 4.13 Å
Structure data	44255 9b6d EMDB-44255, PDB-9b6d: Cryo-EM structure of the mouse TRPM8 channel in the ligand-free desensitized state Method: EM (single particle) / Resolution: 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 Method: EM (single particle) / Resolution: 2.91 Å 44257 9b6f EMDB-44257, PDB-9b6f: Cryo-EM structure of the mouse TRPM8 channel in complex with the antagonist AMG2850 Method: EM (single particle) / Resolution: 3.42 Å 44258 9b6g EMDB-44258, PDB-9b6g: Cryo-EM structure of the mouse TRPM8 channel in complex with the antagonist AMTB Method: EM (single particle) / Resolution: 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 Method: EM (single particle) / Resolution: 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 Method: EM (single particle) / Resolution: 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+ Method: EM (single particle) / Resolution: 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 Method: EM (single particle) / Resolution: 4.13 Å
Chemicals	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
Source	mus musculus (house mouse) parus major (Great Tit)
Keywords	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