title: An O-glycosylated neuroexcitatory conus peptide.
abstract: We purified and characterized a novel peptide from the venom of the fish-hunting cone snail Conus striatus that inhibits voltage-gated K+ channels. The peptide, kappaA-conotoxin SIVA, causes characteristic spastic paralytic symptoms when injected into fish, and in frog nerve-muscle preparations exposed to the toxin, repetitive action potentials are seen in response to a single stimulus applied to the motor nerve. Other electrophysiological tests on diverse preparations provide evidence that is consistent with the peptide blocking K+ channels. The peptide has three disulfide bonds; the locations of Cys residues indicate that the spastic peptide may be the first and defining member of a new family of Conus peptides, the kappaA-conotoxins, which are structurally related to, but pharmacologically distinct from, the alphaA-conotoxins. This 30 AA tricyclic toxin has several characteristics not previously observed in Conus peptides. In addition to the distinctive biological and physiological activity, a novel biochemical feature is the unusually long linear N-terminal tail (11 residues) which contains one O-glycosylated serine at position 7. This is the first evidence for O-glycosylation as a posttranslational modification in a biologically active Conus peptide.
authors.affiliation: The Clayton Foundation Laboratories for Peptide Biology, The Salk Institute, San Diego, California 92186-5800, USA.
authors.forename: A G
authors.initials: AG
authors.lastname: Craig
authors.forename: G
authors.initials: G
authors.lastname: Zafaralla
authors.forename: L J
authors.initials: LJ
authors.lastname: Cruz
authors.forename: A D
authors.initials: AD
authors.lastname: Santos
authors.forename: D R
authors.initials: DR
authors.lastname: Hillyard
authors.forename: J
authors.initials: J
authors.lastname: Dykert
authors.forename: J E
authors.initials: JE
authors.lastname: Rivier
authors.forename: W R
authors.initials: WR
authors.lastname: Gray
authors.forename: J
authors.initials: J
authors.lastname: Imperial
authors.forename: R G
authors.initials: RG
authors.lastname: DelaCruz
authors.forename: A
authors.initials: A
authors.lastname: Sporning
authors.forename: H
authors.initials: H
authors.lastname: Terlau
authors.forename: P J
authors.initials: PJ
authors.lastname: West
authors.forename: D
authors.initials: D
authors.lastname: Yoshikami
authors.forename: B M
authors.initials: BM
authors.lastname: Olivera
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000595:Amino Acid Sequence; D000818:Animals; D001681:Biological Assay; D020916:Conotoxins; D005399:Fishes; D005728:Ganglia, Sympathetic / Q000187:drug effects; D006031:Glycosylation; D013058:Mass Spectrometry; D051379:Mice; D008969:Molecular Sequence Data; D008978:Mollusk Venoms / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D010455:Peptides / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D011898:Ranidae; D012908:Snails; D013035:Spasm / Q000139:chemically induced / Q000503:physiopathology
chemical_list: D020916:Conotoxins; D008978:Mollusk Venoms; D010455:Peptides; C115957:kappaA-conotoxin SIVA