title: Definition of the M-conotoxin superfamily: characterization of novel peptides from molluscivorous Conus venoms.
abstract: Most of the >50,000 different pharmacologically active peptides in Conus venoms belong to a small number of gene superfamilies. In this work, the M-conotoxin superfamily is defined using both biochemical and molecular criteria. Novel excitatory peptides purified from the venoms of the molluscivorous species Conus textile and Conus marmoreus all have a characteristic pattern of Cys residues previously found in the mu-, kappaM-, and psi-conotoxins (CC-C-C-CC). The new peptides are smaller (12-19 amino acids) than the mu-, kappaM-, and psi-conotoxins (22-24 amino acids). One peptide, mr3a, was chemically synthesized in a biologically active form. Analysis of the disulfide bridges of a natural peptide tx3c from C. textile and synthetic peptide mr3a from C. marmoreus showed a novel pattern of disulfide connectivity, different from that previously established for the mu- and psi-conotoxins. Thus, these peptides belong to a new group of structurally and pharmacologically distinct conotoxins that are particularly prominent in the venoms of mollusc-hunting Conus species. Analysis of cDNA clones encoding the novel peptides as well as those encoding mu-, kappaM-, and psi-conotoxins revealed highly conserved amino acid residues in the precursor sequences; this conservation in both amino acid sequence and in the Cys pattern defines a gene superfamily, designated the M-conotoxin superfamily. The peptides characterized can be provisionally assigned to four distinct groups within the M-superfamily based on sequence similarity within and divergence between each group. A notable feature of the superfamily is that two distinct structural frameworks have been generated by changing the disulfide connectivity on an otherwise conserved Cys pattern.
authors.affiliation: Department of Biology, University of Utah, Salt Lake City, Utah 84112, USA.
authors.forename: Gloria P
authors.initials: GP
authors.lastname: Corpuz
authors.forename: Richard B
authors.initials: RB
authors.lastname: Jacobsen
authors.forename: Elsie C
authors.initials: EC
authors.lastname: Jimenez
authors.forename: Maren
authors.initials: M
authors.lastname: Watkins
authors.forename: Craig
authors.initials: C
authors.lastname: Walker
authors.forename: Clark
authors.initials: C
authors.lastname: Colledge
authors.forename: James E
authors.initials: JE
authors.lastname: Garrett
authors.forename: Owen
authors.initials: O
authors.lastname: McDougal
authors.forename: Wenqin
authors.initials: W
authors.lastname: Li
authors.forename: William R
authors.initials: WR
authors.lastname: Gray
authors.forename: David R
authors.initials: DR
authors.lastname: Hillyard
authors.forename: Jean
authors.initials: J
authors.lastname: Rivier
authors.forename: J Michael
authors.initials: JM
authors.lastname: McIntosh
authors.forename: Lourdes J
authors.initials: LJ
authors.lastname: Cruz
authors.forename: Baldomero M
authors.initials: BM
authors.lastname: Olivera
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003001:Cloning, Molecular; D020916:Conotoxins / Q000008:administration & dosage / Q000737:chemistry* / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification; D018076:DNA, Complementary / Q000302:isolation & purification; D004220:Disulfides / Q000737:chemistry; D007276:Injections, Intraventricular; D051379:Mice; D008969:Molecular Sequence Data; D005810:Multigene Family; D010455:Peptides / Q000008:administration & dosage / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification*; D013045:Species Specificity; D021241:Spectrometry, Mass, Electrospray Ionization; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D020916:Conotoxins; D018076:DNA, Complementary; D004220:Disulfides; D010455:Peptides; C485418:conotoxin mr3a, Conus marmoreus