There are two kinds of acetylcholine receptor in nature: nicotinic acetylcholine receptors and muscarinic acetylcholine receptors. We should notice that the mAChRs are not ion channels, but belong instead to the superfamily of G-protein-coupled receptors that activate other ionic channels via a second messenger cascade. So in this page we just talk about the nAChR.
Pentameric ligand-gated ion channel
Pentameric ligand gated ion channels(), or Cys-loop receptors,mediate rapid chemical transmission of signals. Nicotinic acetylcholine receptor is a kind of pentameric ligand gated ion channels. So at first of this page, we introduce some facts of the pentameric ligand gated ion channels, which will help us to understand the structure and function of AChR.
Acetylcholine receptor
The nAChR is unable to bind ACh when bound to any of the snake venom α-neurotoxins. These 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 and death. The nAChR contains two binding sites for snake venom neurotoxins. Progress towards discovering the dynamics of binding action of these sites has proved difficult, although recent studies using normal mode dynamics[13] have aided in predicting the nature of both the binding mechanisms of snake toxins and of ACh to nAChRs. These studies have shown that a twist-like motion caused by ACh binding is likely responsible for pore opening, and that one or two molecules of α-bungarotoxin (or other long-chain α-neurotoxin) suffice to halt this motion. The toxins seem to lock together neighboring receptor subunits, inhibiting the twist and therefore, the opening motion.[1]
Acetylcholine binding protein
The binding site of AChR
The superimposed model of AChBP and α-BTX suggests that the putative agonist HEPES seen in the AChBP structure is blocked from entering or leaving the AChBP interface cleft by the insertion of loop 2 of α-BTX into that cleft.
The possible formation of an intermolecular salt bridge between AChR and α-BTX at that positionmay provide further explanation to the high affinity of binding of the toxin to the receptor.
This notion is supported by recent studies on charge reversal mutations of basic residues on loop 2 of α-neurotoxin.
The possible formation of an intermolecular salt bridge between AChR and α-BTX at that positionmay provide further explanation to the high affinity of binding of the toxin to the receptor.This notion is supported by recent studies on charge reversal mutations of basic residues on loop 2 of α-neurotoxin
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