THE MOLECULAR-BASIS OF CURAREMIMETIC SNAKE NEUROTOXIN SPECIFICITY FOR NEURONAL NICOTINIC RECEPTOR SUBTYPES

Alpha-Bungarotoxin and neuronal bungarotoxin (also known as kappa-bungarotoxin, bungarotoxin 3.1 and toxin F) are the two snake venom neurotoxins used most often to characterize the pharmacology of neuronal nicotinic receptor subtypes. Alpha-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 alpha-subunits in neuronal receptors that are blocked by alpha-bungarotoxin. In alpha-bungarotoxin-insensitive neuronal receptors, the Pro is substituted with Ile. Other amino acid substitutions may also be important. Neuronal bungarotoxin blocks some, but not all, alpha-bungarotoxin sensitive and alpha-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 alpha-bungarotoxin. Non-alpha 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.