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Agonist Selectivity and Ion Permeation in the alpha 3 beta 4 Ganglionic Nicotinic Receptor
Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik. Stockholms universitet, Science for Life Laboratory (SciLifeLab).
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Rekke forfattare: 102019 (engelsk)Inngår i: Neuron, ISSN 0896-6273, E-ISSN 1097-4199, Vol. 104, nr 3, s. 501-511Artikkel i tidsskrift (Fagfellevurdert) 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.

sted, utgiver, år, opplag, sider
2019. Vol. 104, nr 3, s. 501-511
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URN: urn:nbn:se:su:diva-176555DOI: 10.1016/j.neuron.2019.07.030ISI: 000495107500012PubMedID: 31488329OAI: oai:DiVA.org:su-176555DiVA, id: diva2:1379682
Tilgjengelig fra: 2019-12-17 Laget: 2019-12-17 Sist oppdatert: 2020-02-06bibliografisk kontrollert

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