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

Abraham O. Samson, Michael Levitt

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

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 α-bungarotoxin (αBTX) molecules. The toxins seems to lock together neighboring receptor subunits, thereby inhibiting channel opening. Interestingly, one αBTX 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 α-neurotoxins.

Original languageEnglish
Pages (from-to)4065-4070
Number of pages6
JournalBiochemistry
Volume47
Issue number13
DOIs
StatePublished - 1 Apr 2008
Externally publishedYes

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