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Biochemistry. 2008 Apr 1;47(13):4065-70. doi: 10.1021/bi702272j. Epub 2008 Mar 8.

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

Author information

1
Department of Structural Biology, Stanford University, Stanford, California 94305, USA.

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.

PMID:
18327915
PMCID:
PMC2750825
DOI:
10.1021/bi702272j
[Indexed for MEDLINE]
Free PMC Article

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