The Molecular Basis of Curaremimetic Snake Neurotoxin Specificity for Neuronal Nicotinic Receptor Subtypes

Abstract

α-Bungarotoxin and neuronal bungarotoxin (also known as kappabungarotoxin, bungarotoxin 3.1 and toxin F) are the two snake venom neurotoxins used most often to characterize the pharmacology of neuronal nicotinic receptor subtypes. α-Bungarotoxin blocks most muscle nicotinic receptors and some, but not all, cloned or biochemically purified neuronal receptors from the chick, rat, and insect nervous systems. The sequence Cys-Cys-X-X-Pro-Tyr is a motif that is common to all known α-subunits in neuronal receptors that are blocked by α-bungarotoxin. In α-bungatotoxin-insensitive neuronal receptors, the Pro is substituted with He. Other amino acid substitutions may also be important. Neuronal bungarotoxin blocks some, but not all, α-bungarotoxin sensitive and α-bungarotoxin insensitive receptor subtypes expressed in oocytes, and in both vertebrate and invertebrate nervous systems. Both the pharmacology and structure of neuronal bungarotoxin are more complex than those of α-bungarotoxin. Non-α subunits help determine the ability of neuronal bungarotoxin to block functional neuronal receptors. Also, neuronal bungarotoxin is a dimer, and the sequence Ser-Leu-Leu-Cys-Cys, which is conserved in all snake neurotoxins with similar pharmacological properties, is the site of dimerization, as determined by nuclear magnetic resonance (NMR) studies.