Alpha-conotoxin OmIA is a potent ligand for the acetylcholine-binding protein as well as alpha3beta2 and alpha7 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 alpha7 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 alpha7 nAChR subtype when expressed in Xenopus oocytes. Remarkably, the peptide also has high affinity for the alpha3beta2 nAChR indicating that alpha-conotoxin OmIA in combination with the AChBP may serve as a model system for understanding the binding determinants of alpha3beta2 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, alpha3beta2 versus alpha6beta2, and selectively blocks these two subtypes when compared with alpha2beta2, alpha4beta2, and alpha1beta1deltaepsilon nAChRs.
Talley
Todd T
TT
Department of Pharmacology, University of California, La Jolla, California 92093-0636, USA.
Olivera
Baldomero M
BM
Han
Kyou-Hoon
KH
Christensen
Sean B
SB
Dowell
Cheryl
C
Tsigelny
Igor
I
Ho
Kwok-Yiu
KY
Taylor
Palmer
P
McIntosh
J Michael
JM
D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D020916:Conotoxins / Q000737:chemistry / Q000378:metabolism*; D008024:Ligands; D008195:Lymnaea; D008969:Molecular Sequence Data; D011485:Protein Binding; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000737:chemistry / Q000378:metabolism*; D016415:Sequence Alignment; D014981:Xenopus; D064569:alpha7 Nicotinic Acetylcholine Receptor
C428944:AChBP protein, Lymnaea; D002352:Carrier Proteins; D020916:Conotoxins; D008024:Ligands; D021122:Protein Subunits; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor