title: Tyrosine-rich conopeptides affect voltage-gated K+ channels.
abstract: Two venom peptides, CPY-Pl1 (EU000528) and CPY-Fe1 (EU000529), characterized from the vermivorous marine snails Conus planorbis and Conus ferrugineus, define a new class of conopeptides, the conopeptide Y (CPY) family. The peptides have no disulfide cross-links and are 30 amino acids long; the high content of tyrosine is unprecedented for any native gene product. The CPY peptides were chemically synthesized and shown to be biologically active upon injection into both mice and Caenorhabditis elegans; activity on mammalian Kv1 channel isoforms was demonstrated using an oocyte heterologous expression system, and selectivity for Kv1.6 was found. NMR spectroscopy revealed that the peptides were unstructured in aqueous solution; however, a helical region including residues 12-18 for one peptide, CPY-Pl1, formed in trifluoroethanol buffer. Clones obtained from cDNA of both species encoded prepropeptide precursors that shared a unique signal sequence, indicating that these peptides are encoded by a novel gene family. This is the first report of tyrosine-rich bioactive peptides in Conus venom.
authors.affiliation: Department of Biology, University of Utah, Salt Lake City, Utah 84112, USA. imperial@biology.utah.edu
authors.forename: Julita S
authors.initials: JS
authors.lastname: Imperial
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
authors.forename: Annett
authors.initials: A
authors.lastname: Sporning
authors.forename: Heinrich
authors.initials: H
authors.lastname: Terlau
authors.forename: Norelle L
authors.initials: NL
authors.lastname: Daly
authors.forename: David J
authors.initials: DJ
authors.lastname: Craik
authors.forename: Paul F
authors.initials: PF
authors.lastname: Alewood
authors.forename: Baldomero M
authors.initials: BM
authors.lastname: Olivera
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D052078:Conus Snail; D018076:DNA, Complementary / Q000378:metabolism; D051667:Kv1.6 Potassium Channel / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D008978:Mollusk Venoms / Q000378:metabolism; D009865:Oocytes / Q000378:metabolism; D010455:Peptides / Q000737:chemistry*; D024642:Potassium Channels, Voltage-Gated / Q000737:chemistry*; D017386:Sequence Homology, Amino Acid; D013347:Subcellular Fractions; D014270:Trifluoroethanol / Q000737:chemistry; D014443:Tyrosine / Q000737:chemistry*
chemical_list: D018076:DNA, Complementary; D051667:Kv1.6 Potassium Channel; D008978:Mollusk Venoms; D010455:Peptides; D024642:Potassium Channels, Voltage-Gated; D014443:Tyrosine; D014270:Trifluoroethanol