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-Structure paper
タイトル | Agonist Selectivity and Ion Permeation in the α3β4 Ganglionic Nicotinic Receptor. |
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ジャーナル・号・ページ | Neuron, Vol. 104, Issue 3, Page 501-511.e6, Year 2019 |
掲載日 | 2019年11月6日 |
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 / |
PubMed 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. |
リンク | Neuron / PubMed:31488329 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.34 - 4.7 Å |
構造データ | EMDB-20487, PDB-6pv7: EMDB-20488, PDB-6pv8: EMDB-20489: EMDB-20490: |
化合物 | ChemComp-NCT: ChemComp-Y01: ChemComp-NA: ChemComp-NAG: ChemComp-DD9: ChemComp-HOH: ChemComp-P1M: |
由来 |
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キーワード | MEMBRANE PROTEIN (膜タンパク質) / Ligand-gated ion channel (リガンド依存性イオンチャネル) / Nicotinic acetylcholine receptor / Cys-loop receptor |