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Inhibition mechanism of the acetylcholine receptor by alpha-neurotoxins as revealed by normal-mode dynamics.

ABSTRACT: The nicotinic acetylcholine receptor (AChR) is the prototype of ligand-gated ion channels. Here, we calculate the dynamics of the muscle AChR using normal modes. The calculations reveal a twist-like gating motion responsible for channel opening. The ion channel diameter is shown to increase with this twist motion. Strikingly, the twist motion and the increase in channel diameter are not observed for the AChR in complex with two alpha-bungarotoxin (alphaBTX) molecules. The toxins seems to lock together neighboring receptor subunits, thereby inhibiting channel opening. Interestingly, one alphaBTX molecule suffices to prevent the twist motion. These results shed light on the gating mechanism of the AChR and present a complementary inhibition mechanism by snake-venom-derived alpha-neurotoxins.

SUBMITTER: Samson AO

PROVIDER: S-EPMC2750825 | biostudies-literature | 2008 Apr

REPOSITORIES: biostudies-literature

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Inhibition mechanism of the acetylcholine receptor by alpha-neurotoxins as revealed by normal-mode dynamics.

Samson Abraham O AO Levitt Michael M

Biochemistry 20080308 13

The nicotinic acetylcholine receptor (AChR) is the prototype of ligand-gated ion channels. Here, we calculate the dynamics of the muscle AChR using normal modes. The calculations reveal a twist-like gating motion responsible for channel opening. The ion channel diameter is shown to increase with this twist motion. Strikingly, the twist motion and the increase in channel diameter are not observed for the AChR in complex with two alpha-bungarotoxin (alphaBTX) molecules. The toxins seems to lock to ...[more]

PMID: 18327915

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