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

We have determined the crystal structure at 1.8 Angstrom resolution of a co mplex of alpha -bungarotoxin with a high affinity 13-residue peptide that i s homologous to the binding region of the alpha subunit of acetylcholine re ceptor. The peptide fits snugly to the toxin and adopts a beta hairpin conf ormation. The structures of the bound peptide and the homologous loop of ac etylcholine binding protein, a soluble analog of the extracellular domain o f acetylcholine receptor, are remarkably similar. Their superposition indic ates that the toxin wraps around the receptor binding site loop, and in add ition, 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 activ ity.