Mechanism
α-Neurotoxins antagonistically bind tightly and noncovalently to nAChRs of skeletal muscles, thereby blocking the action of ACh at the postsynaptic membrane, inhibiting ion flow and leading to paralysis. nAChRs contain two binding sites for snake venom neurotoxins. Progress towards elucidation of the dynamics of binding action of these sites has proved difficult, although recent studies using normal mode dynamics have aided in predicting the nature of both the binding mechanisms of snake toxins and of ACh to nAChRs.
One such study, by Samson and Levitt, 2008, revealed a twist-like gating motion responsible for nAChR channel opening. The ion channel diameter was shown to increase with this motion, although neither the twist nor the increase in channel diameter was observed when the nAChR was in complex with either one or two α-bungarotoxin molecules. The twist-like motion is in agreement with time-resolved electron microscopic analysis of the acetylcholine receptor pore that shows rotation of the two α subunits upon ACh binding. The fact that only one toxin suffices to inhibit channel opening also correlates with experimental data on the amount of toxin per receptor.
Read more about this topic: Alpha-Bungarotoxin
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