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	Structural mechanisms of α7 nicotinic receptor allosteric modulation and activation.
Journal, issue, pages	Cell, Vol. 187, Issue 5, Page 1160-1176.e21, Year 2024
Publish date	Feb 29, 2024
Authors	Sean M Burke / Mariia Avstrikova / Colleen M Noviello / Nuriya Mukhtasimova / Jean-Pierre Changeux / Ganesh A Thakur / Steven M Sine / Marco Cecchini / Ryan E Hibbs /
PubMed Abstract	The α7 nicotinic acetylcholine receptor is a pentameric ligand-gated ion channel that plays an important role in cholinergic signaling throughout the nervous system. Its unique physiological ...The α7 nicotinic acetylcholine receptor is a pentameric ligand-gated ion channel that plays an important role in cholinergic signaling throughout the nervous system. Its unique physiological characteristics and implications in neurological disorders and inflammation make it a promising but challenging therapeutic target. Positive allosteric modulators overcome limitations of traditional α7 agonists, but their potentiation mechanisms remain unclear. Here, we present high-resolution structures of α7-modulator complexes, revealing partially overlapping binding sites but varying conformational states. Structure-guided functional and computational tests suggest that differences in modulator activity arise from the stable rotation of a channel gating residue out of the pore. We extend the study using a time-resolved cryoelectron microscopy (cryo-EM) approach to reveal asymmetric state transitions for this homomeric channel and also find that a modulator with allosteric agonist activity exploits a distinct channel-gating mechanism. These results define mechanisms of α7 allosteric modulation and activation with implications across the pentameric receptor superfamily.
External links	Cell / PubMed:38382524 / PubMed Central
Methods	EM (single particle)
Resolution	2.19 - 3.31 Å
Structure data	42526 8ut1 EMDB-42526, PDB-8ut1: Alpha7-nicotinic acetylcholine receptor bound to epibatidine Method: EM (single particle) / Resolution: 2.3 Å 42537 8utb EMDB-42537, PDB-8utb: Alpha7-nicotinic acetylcholine receptor bound to epibatidine and NS-1738 Method: EM (single particle) / Resolution: 2.3 Å 42841 8uzj EMDB-42841, PDB-8uzj: Alpha7-nicotinic acetylcholine receptor bound to epibatidine and ivermectin Method: EM (single particle) / Resolution: 2.3 Å 43012 8v80 EMDB-43012, PDB-8v80: Alpha7-nicotinic acetylcholine receptor bound to epibatidine and (-)-TQS Method: EM (single particle) / Resolution: 2.34 Å 43015 8v82 EMDB-43015, PDB-8v82: Alpha7-nicotinic acetylcholine receptor bound to epibatidine and PNU-120596 Method: EM (single particle) / Resolution: 2.61 Å 43025 8v86 EMDB-43025, PDB-8v86: Alpha7-nicotinic acetylcholine receptor bound to GAT107 Method: EM (single particle) / Resolution: 2.47 Å 43030 8v88 EMDB-43030, PDB-8v88: Alpha7-nicotinic acetylcholine receptor bound to epibatidine and GAT107 Method: EM (single particle) / Resolution: 2.3 Å 43031 8v89 EMDB-43031, PDB-8v89: Alpha7-nicotinic acetylcholine receptor time resolved resting state Method: EM (single particle) / Resolution: 2.53 Å 43032 8v8a EMDB-43032, PDB-8v8a: Alpha7-nicotinic acetylcholine receptor time resolved bound to epibatidine and PNU-120596 desensitized intermediate state Method: EM (single particle) / Resolution: 2.19 Å 43034 8v8c EMDB-43034, PDB-8v8c: Alpha7-nicotinic acetylcholine receptor time resolved bound to epibatidine and PNU-120596 asymmetric state 1 Method: EM (single particle) / Resolution: 3.29 Å 43035 8v8d EMDB-43035, PDB-8v8d: Alpha7-nicotinic acetylcholine receptor time resolved bound to epibatidine and PNU-120596 asymmetric state 2 Method: EM (single particle) / Resolution: 3.31 Å
Chemicals	ChemComp-CA: Unknown entry ChemComp-NAG: 2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine ChemComp-POV: (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate / phospholipidYM / POPC ChemComp-9Z9: (3beta,14beta,17beta,25R)-3-[4-methoxy-3-(methoxymethyl)butoxy]spirost-5-en / detergentYM ChemComp-EPJ: EPIBATIDINE / alkaloidYM / Epibatidine ChemComp-HOH: WATER / Water ChemComp, No image ChemComp-XG3: Unknown entry ChemComp-IVM: (2aE,4E,5'S,6S,6'R,7S,8E,11R,13R,15S,17aR,20R,20aR,20bS)-6'-[(2S)-butan-2-yl]-20,20b-dihydroxy-5',6,8,19-tetramethyl-17 / antiparasiticYM / Ivermectin ChemComp, No image ChemComp-YLR: Unknown entry ChemComp-I34: N-(5-Chloro-2,4-dimethoxyphenyl)-N'-(5-methyl-3-isoxazolyl)-urea / PNU-120,596 ChemComp, No image ChemComp-YLI: Unknown entry ChemComp-R16: HEXADECANE / Hexadecane
Source	homo sapiens (human) escherichia coli (E. coli)
Keywords	MEMBRANE PROTEIN / Ion channel / modulator / PAM / NICOTINIC RECEPTOR