title: An hypothesis concerning the molecular structure of the nicotinic acetylcholine receptor.
abstract: 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.
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000595:Amino Acid Sequence; D000664:Amphibian Venoms / Q000378:metabolism; D001665:Binding Sites; D003472:Curare / Q000378:metabolism; D008956:Models, Chemical; D010880:Piperidines / Q000378:metabolism; D011487:Protein Conformation; D000644:Quaternary Ammonium Compounds / Q000378:metabolism; D011796:Quinacrine / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000378:metabolism*
chemical_list: D000664:Amphibian Venoms; D010880:Piperidines; D000644:Quaternary Ammonium Compounds; D011950:Receptors, Cholinergic; D011978:Receptors, Nicotinic; D003472:Curare; D011796:Quinacrine; D000109:Acetylcholine; C007948:histrionicotoxin