Characterization of α-conotoxin interactions with the nicotinic acetylcholine receptor and monoclonal antibodies

The venoms of predatory marine cone snails, Conus species, contain numerous peptides and proteins with remarkably diverse pharmacological properties. One group of peptides are the α­ conotoxins, which consist of 13–19 amino acids constrained by two disulphide bonds. A biologically active fluorescein derivative of Conus geographus α-conotoxin GI (FGI) was used in novel solution-phase-binding assays with purified Torpedo californica nicotinic acetylcholine receptor (nAchR) and monoclonal anti­ bodies developed against the toxin. The binding of FGI to nAchR or antibody had apparent dissociation constants of 10–100 nM. Structure–function studies with α-conotoxin GI analogues composed of a single disulphide loop revealed that different conformational restraints are necessary for effective toxin interactions with nAchR or antibodies.