title: Purification and characterization of a novel excitatory peptide from Conus distans venom that defines a novel gene superfamily of conotoxins.
abstract: An excitatory peptide, di16a, with 49 amino acids and 10 cysteine residues was purified and characterized from the venom of Conus distans. Five AA residues were modified: one gamma-carboxyglutamate (Gla), and four hydroxyproline (Hyp) residues. A cDNA clone encoding the precursor for the peptide was characterized; the peptide has a novel cysteine framework and a distinctive signal sequence that differs from any other conotoxin superfamily. The peptide was chemically synthesized and folded, and synthetic and native materials were shown to co-elute. Injection of the synthetic peptide causes a hyperexcitable phenotype in mice greater than 3 weeks of age at lower doses, and lethargy at higher doses. The peptide defines both a previously uncharacterized gene superfamily of conopeptides, and a new Cys pattern with three vicinal Cys residues.
authors.affiliation: Department of Biology, University of Utah, 257 South, 1400 East, Salt Lake City, UT 84112, USA. pc15@utah.edu
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
authors.forename: James E
authors.initials: JE
authors.lastname: Garrett
authors.forename: Maren
authors.initials: M
authors.lastname: Watkins
authors.forename: Baldomero M
authors.initials: BM
authors.lastname: Olivera
mesh_terms: D000367:Age Factors; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D020916:Conotoxins / Q000235:genetics*; D018076:DNA, Complementary / Q000737:chemistry; D051379:Mice; D008969:Molecular Sequence Data; D008978:Mollusk Venoms / Q000032:analysis*; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification* / Q000633:toxicity
chemical_list: D020916:Conotoxins; D018076:DNA, Complementary; D008978:Mollusk Venoms; D010455:Peptides