The structure of a peptide corresponding to residues 182-202 of the acetylcholine receptor α1 subunit in complex with α-bungarotoxin was solved using NMR spectroscopy. The peptide contains the complete sequence of the major determinant of AChR involved in α-bungarotoxin binding. One face of the long β hairpin formed by the AChR peptide consists of exposed nonconserved residues, which interact extensively with the toxin. Mutations of these receptor residues confer resistance to the toxin. Conserved AChR residues form the opposite face of the β hairpin, which creates the inner and partially hidden pocket for acetylcholine. An NMR-derived model for the receptor complex with two α-bungarotoxin molecules shows that this pocket is occupied by the conserved α-neurotoxin residue R36, which forms cation-π interactions with both αW149 and γW55/δW57 of the receptor and mimics acetylcholine.
Bibliographical noteFunding Information:
We thank Mrs. Aviva Kapitkovski and Mr. Yehezkiel Haik for synthesizing and purifying the AChR peptides. This study was supported by a US-Israel Binational Science Foundation grant 98-328 to J.A. J.A. is the Dr. Joseph and Ruth Owades Professor of Chemistry.