α-Conotoxin OmIA is a potent ligand for the acetylcholine-binding protein as well as α3β2 and α7 nicotinic acetylcholine receptors

The molluskan acetylcholine-binding protein ( AChBP) is a homolog of the extracellular binding domain of the pentameric ligand-gated ion channel family. AChBP most closely resembles the alpha-subunit of nicotinic acetylcholine receptors and in particular the homomeric alpha 7 nicotinic receptor. We report the isolation and characterization of an alpha-conotoxin that has the highest known affinity for the Lymnaea AChBP and also potently blocks the alpha 7 nAChR subtype when expressed in Xenopus oocytes. Remarkably, the peptide also has high affinity for the alpha 3 beta 2 nAChR indicating that alpha-conotoxin OmIA in combination with the AChBP may serve as a model system for understanding the binding determinants of alpha 3 beta 2 nAChRs. alpha-Conotoxin OmIA was purified from the venom of Conus omaria. It is a 17-amino-acid, two-disulfide bridge peptide. The ligand is the first alpha-conotoxin with higher affinity for the closely related receptor subtypes, alpha 3 beta 2 versus alpha 6 beta 2, and selectively blocks these two subtypes when compared with alpha 2 beta 2, alpha 4 beta 2, and alpha 1 beta 1 delta epsilon nAChRs.