An hypothesis concerning the molecular structure of the nicotinic acetylcholine receptor.

An hypothesis is presented concerning the molecular structure of the nicotinic acetylcholine receptor at the neuromuscular junction based on the actual amino acid sequence of the N-terminal segment of the alpha-subunit and the Chou and Fasman prediction of secondary structure from the primary sequence. This is mainly in the form of two alpha-helices cross-linked by four ionically bound complementary amino acids (arg/lys to glu). This structure (R) is complementary to a wide range of ACh agonists and to the antagonist beta-erythroidine. If the ionic cross-links are disrupted the two segments can separate by 2-3 A. This new conformation (R1) is now complementary to antagonists of the type of histrionicotoxin. A further separation (approximately 8 A) gives a conformation complementary to antagonist of the type of decamethonium. Experiments to test the hypothesis are suggested.