title: A diverse family of novel peptide toxins from an unusual cone snail, Conus californicus.
abstract: Diversity among Conus toxins mirrors the high species diversity in the Indo-Pacific region, and evolution of both is thought to stem from feeding-niche specialization derived from intra-generic competition. This study focuses on Conus californicus, a phylogenetic outlier endemic to the temperate northeast Pacific. Essentially free of congeneric competitors, it preys on a wider variety of organisms than any other cone snail. Using molecular cloning of cDNAs and mass spectrometry, we examined peptides isolated from venom ducts to elucidate the sequences and post-translational modifications of two eight-cysteine toxins (cal12a and cal12b of type 12 framework) that block voltage-gated Na(+) channels. Based on homology of leader sequence and mode of action, these toxins are related to the O-superfamily, but differ significantly from other members of that group. Six of the eight cysteine residues constitute the canonical framework of O-members, but two additional cysteine residues in the N-terminal region define an O+2 classification within the O-superfamily. Fifteen putative variants of Cal12.1 toxins have been identified by mRNAs that differ primarily in two short hypervariable regions and have been grouped into three subtypes (Cal12.1.1-3). This unique modular variation has not been described for other Conus toxins and suggests recombination as a diversity-generating mechanism. We propose that these toxin isoforms show specificity for similar molecular targets (Na(+) channels) in the many species preyed on by C. californicus and that individualistic utilization of specific toxin isoforms may involve control of gene expression.
authors.affiliation: Hopkins Marine Station, Stanford University, Pacific Grove, CA 93950, USA.
authors.forename: W F
authors.initials: WF
authors.lastname: Gilly
authors.forename: T A
authors.initials: TA
authors.lastname: Richmond
authors.forename: T F
authors.initials: TF
authors.lastname: Duda
authors.forename: C
authors.initials: C
authors.lastname: Elliger
authors.forename: Z
authors.initials: Z
authors.lastname: Lebaric
authors.forename: J
authors.initials: J
authors.lastname: Schulz
authors.forename: J P
authors.initials: JP
authors.lastname: Bingham
authors.forename: J V
authors.initials: JV
authors.lastname: Sweedler
mesh_terms: D000818:Animals; D001483:Base Sequence; D002140:California; D003001:Cloning, Molecular; D052078:Conus Snail / Q000737:chemistry*; D017931:DNA Primers / Q000235:genetics; D004594:Electrophysiology; D015723:Gene Library; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D008978:Mollusk Venoms / Q000032:analysis / Q000145:classification / Q000235:genetics*; D010140:Pacific Ocean; D010455:Peptides / Q000032:analysis / Q000145:classification / Q000235:genetics*; D017422:Sequence Analysis, DNA; D026941:Sodium Channel Blockers / Q000633:toxicity*
chemical_list: D017931:DNA Primers; D008978:Mollusk Venoms; D010455:Peptides; D026941:Sodium Channel Blockers