A New Family of Conus Peptides Targeted to the Nicotinic Acetylcholine Receptor (∗)

• Published in: The Journal of biological chemistry 1995-09, Vol.270 (38), p.22361-22367
• Main Authors: Hopkins, Chris, Grilley, Michelle, Miller, Charleen, Shon, Ki-Joon, Cruz, Lourdes J., Gray, William R., Dykert, John, Rivier, Jean, Yoshikami, Doju, Olivera, Baldomero M.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Conotoxins; Conus purpurascens; Gastropoda; Marine; Molecular Sequence Data; Mollusk Venoms - isolation & purification; Mollusk Venoms - pharmacology; Peptides, Cyclic - chemical synthesis; Peptides, Cyclic - isolation & purification; Peptides, Cyclic - pharmacology; Receptors, Nicotinic - drug effects; Snails - chemistry; Structure-Activity Relationship
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.270.38.22361

In this work, a new family of Conus peptides, the αA-conotoxins, which target the nicotinic acetylcholine receptor, is defined. The first members of this family have been characterized from the eastern Pacific species, Conus purpurascens (the purple cone); three peptides that cause paralysis in fish were purified and characterized from milked venom. The sequence and disulfide bonding pattern of one of these, αA-conotoxin PIVA, is as follows: where O represents trans-4-hydroxyproline. The two other peptides purified from C. purpurascens venom are the under-hydroxylated derivatives, αA-conotoxin PIVA and [Pro7,13]αA-conotoxin PIVA. The peptides have been chemically synthesized in a biologically active form. Both electrophysiological experiments and competition binding with α-bungarotox- in demonstrate that αA-PIVA acts as an antagonist of the nicotinic acetylcholine receptor at the postsynaptic membrane.