A Novel Dimeric Conotoxin, FrXXA, from the Vermivorous Cone Snail Conus fergusoni, of the Eastern Pacific, Inhibits Nicotinic Acetylcholine Receptors

We isolated a new dimeric conotoxin with inhibitory activity against neuronal nicotinic acetylcholine receptors. Edman degradation and transcriptomic studies indicate a homodimeric conotoxin composed by two chains of 47 amino acid in length. It has the cysteine framework XX and 10 disulfide bonds. According to conotoxin nomenclature, it has been named as alpha D-FrXXA. The alpha D-FrXXA conotoxin inhibited the ACh-induced response on nAChR with a IC50 of 125 nM on h alpha 7, 282 nM on h alpha 3 beta 2, 607 nM on alpha 4 beta 2, 351 nM on mouse adult muscle, and 447 nM on mouse fetal muscle. This is first toxin characterized from C. fergusoni and, at the same time, the second alpha D-conotoxin characterized from a species of the Eastern Pacific.