Solution conformation of a neuronal nicotinic acetylcholine receptor antagonist α-conotoxin OmIA that discriminates α3 vs. α6 nAChR subtypes

Abstract

α-Conotoxin OmIA from Conus omaria is the only α-conotoxin that shows a ∼20-fold higher affinity to the α3β2 over the α6β2 subtype of nicotinic acetylcholine receptor. We have determined a three-dimensional structure of α-conotoxin OmIA by nuclear magnetic resonance spectroscopy. α-Conotoxin OmIA has an "ω-shaped" overall topology with His5-Asn12 forming an α-helix. Structural features of α-conotoxin OmIA responsible for its selectivity are suggested by comparing its surface characteristics with other functionally related α4/7 subfamily conotoxins. Reduced size of the hydrophilic area in α-conotoxin OmIA seems to be associated with the reduced affinity towards the α6β2 nAChR subtype.