A model for short alpha-neurotoxin bound to nicotinic acetylcholine receptor from Torpedo californica.
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.
Mordvintsev
Dmitry Y
DY
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, GSP-7, 117997 Moscow, Russia. Chlorine@yandex.ru
Polyak
Yakov L
YL
Kuzmine
Dmitry A
DA
Levtsova
Olga V
OV
Tourleigh
Yegor V
YV
Kasheverov
Igor E
IE
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
D004546:Elapid Venoms; D009498:Neurotoxins; D011978:Receptors, Nicotinic