Conotoxin MI inhibits the alpha-delta acetylcholine binding site of the Torpedo marmorata receptor.
The muscle-type nicotinic receptor has two pharmacologically distinguishable acetylcholine binding sites at the alpha-gamma and alpha-delta subunit interfaces; alpha-conotoxins can bind them selectively. As reported, alpha-conotoxin MI has greater affinity for the site near the alpha-delta interface of the BC(3)H1 cell receptor but, in the case of the Torpedo californica receptor, displays greater affinity for that near the alpha-gamma interface. To further investigate ligand selectivity, we study the conotoxin MI-Torpedo marmorata receptor interaction. In this work, we show the binding of alpha-conotoxin MI to the T. marmorata receptor and the influence of the antagonist alpha-Bungarotoxin and the agonist carbamylcholine on such binding; in addition, and contrasting with the results for the Torpedo californica receptor, we identify the alpha-delta subunit interface as the high affinity binding site. This is the first work describing different characteristics of the interaction between alpha-conotoxin MI and receptors from different species of the same genus.
Departamento de Química Biológica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires (UBA-CONICET), Instituto de Química y Fisicoquímica Biológicas, Junín 956, Buenos Aires, Argentina.
Leonardo M
LM
Cortez
Sergio G
SG
del Canto
Fernando D
FD
Testai
Mirtha J
MJ
Biscoglio de Jiménez Bonino
D000109:Acetylcholine / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D002038:Bungarotoxins / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D020916:Conotoxins / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D011485:Protein Binding; D011978:Receptors, Nicotinic / Q000737:chemistry* / Q000378:metabolism; D013045:Species Specificity; D014101:Torpedo / Q000378:metabolism*
D002038:Bungarotoxins; D020916:Conotoxins; D011978:Receptors, Nicotinic; C036155:conotoxin MI; D002217:Carbachol; D000109:Acetylcholine