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Agonist Selectivity and Ion Permeation in the alpha 3 beta 4 Ganglionic Nicotinic Receptor
Univ Texas Southwestern Med Ctr Dallas, Dept Neurosci, Dallas, TX 75390 USA..ORCID iD: 0000-0002-4458-359X
Univ Texas Southwestern Med Ctr Dallas, Dept Neurosci, Dallas, TX 75390 USA..
Stockholm Univ, Dept Biochem & Biophys, Sci Life Lab, S-17121 Solna, Sweden..
Univ Texas Southwestern Med Ctr Dallas, Dept Neurosci, Dallas, TX 75390 USA..
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2019 (English)In: Neuron, ISSN 0896-6273, E-ISSN 1097-4199, Vol. 104, no 3, p. 501-+Article in journal (Refereed) Published
Abstract [en]

Nicotinic acetylcholine receptors are pentameric ion channels that mediate fast chemical neurotransmission. The alpha 3 beta 4 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 alpha 3 beta 4 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 alpha 3 beta 4-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.

Place, publisher, year, edition, pages
CELL PRESS , 2019. Vol. 104, no 3, p. 501-+
National Category
Basic Medicine
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URN: urn:nbn:se:kth:diva-264322DOI: 10.1016/j.neuron.2019.07.030ISI: 000495107500012PubMedID: 31488329Scopus ID: 2-s2.0-85074236074OAI: oai:DiVA.org:kth-264322DiVA, id: diva2:1374560
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QC 20191202

Available from: 2019-12-02 Created: 2019-12-02 Last updated: 2019-12-19Bibliographically approved

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Lindahl, Erik

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