Alpha S-conotoxin RVIIIA: a structurally unique conotoxin that broadly targets nicotinic acetylcholine receptors.
We report the purification and characterization of a new conotoxin from the venom of Conus radiatus. The peptide, alphaS-conotoxin RVIIIA (alphaS-RVIIIA), is biochemically unique with respect to its amino acid sequence, post-translational modification, and molecular targets. In comparison to other nicotinic antagonists from Conus venoms, alphaS-RVIIIA exhibits an unusually broad targeting specificity for nicotinic acetylcholine receptor (nAChR) subtypes, as assayed by electrophysiology. The toxin is paralytic to mice and fish, consistent with its nearly irreversible block of the neuromuscular nAChR. Similar to other antagonists of certain neuronal nAChRs, the toxin also elicits seizures in mice upon intracranial injection. The only previously characterized conotoxin from the S superfamily, sigma-conotoxin GVIIIA, is a specific competitive antagonist of the 5-HT3 receptor; thus, alphaS-RVIIIA defines a novel family of nicotinic antagonists within the S superfamily. All previously characterized competitive conotoxin nAChR antagonists have been members of the A superfamily of conotoxins. Our working hypothesis is that the particular group of fish-hunting Conus species that includes Conus radiatus uses the alphaS-conotoxin family to target the muscle nAChR and paralyze prey.
Teichert
Russell W
RW
Department of Biology, University of Utah, Salt Lake City, Utah 84112, USA. teichert@biology.utah.edu
Jimenez
Elsie C
EC
Olivera
Baldomero M
BM
D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans; D020916:Conotoxins / Q000008:administration & dosage* / Q000737:chemistry* / Q000302:isolation & purification; D006054:Goldfish; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D018733:Nicotinic Antagonists / Q000008:administration & dosage* / Q000737:chemistry* / Q000302:isolation & purification; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D010455:Peptides / Q000008:administration & dosage / Q000138:chemical synthesis; D011978:Receptors, Nicotinic / Q000378:metabolism*; D012640:Seizures / Q000139:chemically induced; D017386:Sequence Homology, Amino Acid; D014981:Xenopus; D064569:alpha7 Nicotinic Acetylcholine Receptor
C579167:Chrna7 protein, human; C579166:Chrna7 protein, mouse; D020916:Conotoxins; D018733:Nicotinic Antagonists; D010455:Peptides; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C502789:alphaS-conotoxin RVIIIA, Conus radiatus