Ligand Binding at the 4-4 Agonist-Binding Site of the 42 nAChR Triggers Receptor Activation through a Pre-Activated Conformational State

• Published in: PloS one Vol. 11; no. 8; p. e0161154
• Main Authors: Indurthi, Dinesh C, Lewis, Trevor M, Ahring, Philip K, Balle, Thomas, Chebib, Mary, Absalom, Nathan L
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 23.08.2016; Public Library of Science (PLoS)
• Subjects: Acetylcholine - metabolism; Acetylcholine - pharmacology; Acetylcholine receptors; Animals; Azetidines - pharmacology; Binding Sites; Brain research; Cell Membrane - drug effects; Cell Membrane - genetics; Humans; Ion Channel Gating - genetics; Ligand binding (Biochemistry); Ligands; Molecular Conformation - drug effects; Oocytes - drug effects; Oocytes - growth & development; Oocytes - metabolism; Oxadiazoles - pharmacology; Properties; Protein Binding; Protein Isoforms - drug effects; Pyridines - pharmacology; Receptors, Nicotinic - genetics; Receptors, Nicotinic - metabolism; Testing; Xenopus laevis - genetics; Xenopus laevis - growth & development

The α4β2 nicotinic acetylcholine receptor (nAChR) is the most abundant subtype in the brain and exists in two functional stoichiometries: (α4)3(β2)2 and (α4)2(β2)3. A distinct feature of the (α4)3(β2)2 receptor is the biphasic activation response to the endogenous agonist acetylcholine, where it is...