The binding site of acetylcholine receptor as visualized in the X-ray structure of a complex between α-bungarotoxin and a mimotope peptide

Michal Harel, Roni Kasher, Anne Nicolas, J. Mitchell Guss, Moshe Balass, Mati Fridkin, August B. Smit, Katjuša Brejc, Titia K. Sixma, Ephraim Katchalski-Katzir, Joel L. Sussman, Sara Fuchs

Research output: Contribution to journalArticlepeer-review

107 Scopus citations

Abstract

We have determined the crystal structure at 1.8 Å resolution of a complex of α-bungarotoxin with a high affinity 13-residue peptide that is homologous to the binding region of the α subunit of acetylcholine receptor. The peptide fits snugly to the toxin and adopts a β hairpin conformation. The structures of the bound peptide and the homologous loop of acetylcholine binding protein, a soluble analog of the extracellular domain of acetylcholine receptor, are remarkably similar. Their superposition indicates that the toxin wraps around the receptor binding site loop, and in addition, binds tightly at the interface of two of the receptor subunits where it inserts a finger into the ligand binding site, thus blocking access to the acetylcholine binding site and explaining its strong antagonistic activity.

Original languageEnglish
Pages (from-to)265-275
Number of pages11
JournalNeuron
Volume32
Issue number2
DOIs
StatePublished - 25 Oct 2001
Externally publishedYes

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