Snake α-Neurotoxins with Different Affinity to Two Binding Sites of Muscle-Type Nicotinic Acetylcholine Receptors

Nicotinic acetylcholine receptors (nAChRs) are the ligand-gated ionic channels consisting of five homologous subunits, which form transmembrane pore. Pharmacologically different types of nAChRs exist because of differences in the subunit composition. Muscle-type nAChRs contain two binding sites, which differ in their subunit composition. Both sites interact with α-neurotoxins (α-NTs) from snake venom with high affinity. Most α-NTs bind to both sites with similar affinity. However, there are several α-NTs with different affinity to two binding sites of muscle-type nAChR. In this study, we found that neurotoxin I from the venom of the Naja oxiana cobra also distinguishes between the two binding sites of muscle-type nAChR. Based on the analysis of known amino acid sequences of snake α-NTs, it is assumed that there are several more toxins with such properties. These toxins can be used as molecular tools to study subtle differences in the mechanisms of ligand recognition in the binding sites of muscle-type nAChRs.