title: Probing new components (loop G and the α-α interface) of neonicotinoid binding sites on nicotinic acetylcholine receptors.
abstract: Neonicotinoid insecticides interact with the orthosteric site on the extracellular ligand binding domain (LBD) of nicotinic acetylcholine receptors (nAChRs), typically activating the cation permeable ion channels. In nAChRs consisting of two α and three non-α subunits, LBDs contain six loops (loops A, B and C on the α subunit and loops D, E and F on the non-α subunit) which make up the orthosteric binding site at the α/non-α subunit interfaces. Recently, an additional site (loop G) on the β1 strand has been identified. Also, when the α/non-α subunit ratio is 3/2, another binding site is generated at the interface of two adjacent α subunits. Roles for loop G and the α-α interface in the interactions with neonicotinoids are discussed with reference to recent structural and physiological data.
authors.affiliation: Department of Applied Biological Chemistry, Faculty of Agriculture, Kinki University, 3327-204 Nakamachi, Nara 631-8505, Japan. Electronic address: makoto_i@nara.kindai.ac.jp.
authors.forename: Makoto
authors.initials: M
authors.lastname: Ihara
authors.affiliation: The Wolfson Institute for Biomedical Research, Department of Medicine, University College London, Cruciform Building, Gower Street, London, WC1E 6BT, UK.
authors.forename: David B
authors.initials: DB
authors.lastname: Sattelle
authors.affiliation: Department of Applied Biological Chemistry, Faculty of Agriculture, Kinki University, 3327-204 Nakamachi, Nara 631-8505, Japan. Electronic address: kmatsuda@nara.kindai.ac.jp.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Matsuda
mesh_terms: D000818:Animals; D001665:Binding Sites; D018360:Crystallography, X-Ray; D019476:Insect Proteins / Q000737:chemistry / Q000378:metabolism*; D007306:Insecticides / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000737:chemistry / Q000378:metabolism*
chemical_list: D019476:Insect Proteins; D007306:Insecticides; D018722:Nicotinic Agonists; D021122:Protein Subunits; D011978:Receptors, Nicotinic
keywords: Acetylcholine binding protein; Ion channel; Ligand binding loops (A, B, C, D, E, F and G); Neonicotinoid; Nicotinic acetylcholine receptor; α–α interface