title: A model for short alpha-neurotoxin bound to nicotinic acetylcholine receptor from Torpedo californica.
abstract: Short- and long-chain alpha-neurotoxins from snake venoms are potent blockers of nicotinic acetylcholine receptors (nAChRs). Short alpha-neurotoxins consist of 60-62 amino acid residues and include 4 disulfide bridges, whereas long alpha-neurotoxins have 66-75 residues and 5 disulfides. The spatial structure of these toxins is built by three loops, I-III "fingers," confined by four disulfide bridges; the fifth disulfide of long-chain alpha-neurotoxins is situated close to the tip of central loop II. An accurate knowledge of the mode of alpha-neurotoxin-nAChR interaction is important for rational design of new nAChR agonists and antagonists for medical purposes. Ideas on the topography of toxin-nAChR complexes were based until recently on nAChR interactions with selectively labeled alpha-neurotoxins, mutations in toxins, nAChR, or both. Recently, crystal structures have been solved for the Torpedo marmorata nAChR (4A[Unwin, 2005]) and for the acetylcholine-binding protein (AChBP) complexed with mollusk alpha-conotoxin (2.4 A[Celie et al., 2005]) or alpha-cobratoxin, long-chain alpha-neurotoxin (4 A [Bourne et al., 2005]). However, there were no angstrom-resolution models for complexes of short-chain alpha-neurotoxins. Here, we report the model of the Torpedo californica nAChR extracellular domain complexed to a short-chain alpha-neurotoxin II (NTII) from Naja oxiana cobra venom.
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, GSP-7, 117997 Moscow, Russia. Chlorine@yandex.ru
authors.forename: Dmitry Y
authors.initials: DY
authors.lastname: Mordvintsev
authors.forename: Yakov L
authors.initials: YL
authors.lastname: Polyak
authors.forename: Dmitry A
authors.initials: DA
authors.lastname: Kuzmine
authors.forename: Olga V
authors.initials: OV
authors.lastname: Levtsova
authors.forename: Yegor V
authors.initials: YV
authors.lastname: Tourleigh
authors.forename: Igor E
authors.initials: IE
authors.lastname: Kasheverov
mesh_terms: D000818:Animals; D004546:Elapid Venoms / Q000493:pharmacokinetics / Q000633:toxicity; D008954:Models, Biological; D009498:Neurotoxins / Q000493:pharmacokinetics*; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism*; D014101:Torpedo
chemical_list: D004546:Elapid Venoms; D009498:Neurotoxins; D011978:Receptors, Nicotinic