Conotoxin MI inhibits the α–δ acetylcholine binding site of the Torpedo marmorata receptor

• Published in: Biochemical and biophysical research communications 2002-07, Vol.295 (4), p.791-795
• Main Authors: Cortez, Leonardo M, del Canto, Sergio G, Testai, Fernando D, Biscoglio de Jiménez Bonino, Mirtha J
• Format: Article
• Language: English
• Subjects: Acetylcholine - chemistry; Acetylcholine - metabolism; Animals; Binding Sites; Binding, Competitive; Bungarotoxins - pharmacology; Carbachol - pharmacology; Conotoxins - pharmacology; Conus; Dose-Response Relationship, Drug; Electrophoresis, Polyacrylamide Gel; Ligand binding sites; Nicotinic receptors; Protein Binding; Receptors, Nicotinic - chemistry; Receptors, Nicotinic - metabolism; Species Specificity; Torpedo - metabolism; Torpedo marmorata; α-Conotoxin MI
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/S0006-291X(02)00758-1

The muscle-type nicotinic receptor has two pharmacologically distinguishable acetylcholine binding sites at the α–γ and α–δ subunit interfaces; α-conotoxins can bind them selectively. As reported, α-conotoxin MI has greater affinity for the site near the α–δ interface of the BC 3H1 cell receptor but, in the case of the Torpedo californica receptor, displays greater affinity for that near the α–γ interface. To further investigate ligand selectivity, we study the conotoxin MI– Torpedo marmorata receptor interaction. In this work, we show the binding of α-conotoxin MI to the T. marmorata receptor and the influence of the antagonist α-Bungarotoxin and the agonist carbamylcholine on such binding; in addition, and contrasting with the results for the Torpedo californica receptor, we identify the α–δ subunit interface as the high affinity binding site. This is the first work describing different characteristics of the interaction between α-conotoxin MI and receptors from different species of the same genus.