National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
T32GM008203
米国
National Institutes of Health/National Institute on Drug Abuse (NIH/NIDA)
T32DA07290
米国
National Institutes of Health/National Institute on Drug Abuse (NIH/NIDA)
DA042072
米国
National Institutes of Health/National Institute on Drug Abuse (NIH/NIDA)
DA037492
米国
National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS)
NS095899
米国
引用
ジャーナル: Neuron / 年: 2019 タイトル: Agonist Selectivity and Ion Permeation in the α3β4 Ganglionic Nicotinic Receptor. 著者: Anant Gharpure / Jinfeng Teng / Yuxuan Zhuang / Colleen M Noviello / Richard M Walsh / Rico Cabuco / Rebecca J Howard / Nurulain T Zaveri / Erik Lindahl / Ryan E Hibbs / 要旨: Nicotinic acetylcholine receptors are pentameric ion channels that mediate fast chemical neurotransmission. The α3β4 nicotinic receptor subtype forms the principal relay between the central and ...Nicotinic acetylcholine receptors are pentameric ion channels that mediate fast chemical neurotransmission. The α3β4 nicotinic receptor subtype forms the principal relay between the central and peripheral nervous systems in the autonomic ganglia. This receptor is also expressed focally in brain areas that affect reward circuits and addiction. Here, we present structures of the α3β4 nicotinic receptor in lipidic and detergent environments, using functional reconstitution to define lipids appropriate for structural analysis. The structures of the receptor in complex with nicotine, as well as the α3β4-selective ligand AT-1001, complemented by molecular dynamics, suggest principles of agonist selectivity. The structures further reveal much of the architecture of the intracellular domain, where mutagenesis experiments and simulations define residues governing ion conductance.
タンパク質・ペプチド: Fusion protein of Neuronal acetylcholine receptor subunit beta-4 and Soluble cytochrome b562
複合体: IgG2b/kappa antibody
複合体: IgG2b heavy chain
タンパク質・ペプチド: IgG2b Fab heavy chain
複合体: Kappa Fab light chain
タンパク質・ペプチド: Kappa Fab light chain
リガンド: (S)-3-(1-METHYLPYRROLIDIN-2-YL)PYRIDINE
リガンド: CHOLESTEROL HEMISUCCINATE
リガンド: SODIUM ION
リガンド: 2-acetamido-2-deoxy-beta-D-glucopyranose
リガンド: nonane
リガンド: water
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超分子 #1: Human alpha3beta4 nicotinic receptor in complex with Fab fragment...
超分子
名称: Human alpha3beta4 nicotinic receptor in complex with Fab fragments and bound to nicotine タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#4 詳細: Fab fragments generated by proteolytic cleavage of IgG antibody
由来(天然)
生物種: Homo sapiens (ヒト)
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超分子 #2: Human alpha3beta4 nicotinic acetylcholine receptor