A diverse family of novel peptide toxins from an unusual cone snail, Conus californicus

W. F. Gilly, T. A. Richmond, T. F. Duda, C. Elliger, Z. Lebaric, J. Schulz, J. P. Bingham, J. V. Sweedler

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)147-161
Number of pages15
JournalJournal of Experimental Biology
Volume214
Issue number1
DOIs
StatePublished - Jan 1 2011

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Conus Snail
seed cones
peptide
snail
toxin
Cysteine
snails
toxins
peptides
Peptides
Protein Isoforms
cysteine
Snails
Venoms
Molecular Cloning
Post Translational Protein Processing
Sequence Homology
Genetic Recombination
Mass Spectrometry
Complementary DNA

Keywords

  • Conotoxins
  • Peptides
  • Peptidomics
  • Sodium channels

ASJC Scopus subject areas

  • Animal Science and Zoology
  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Physiology
  • Insect Science
  • Aquatic Science

Cite this

A diverse family of novel peptide toxins from an unusual cone snail, Conus californicus. / Gilly, W. F.; Richmond, T. A.; Duda, T. F.; Elliger, C.; Lebaric, Z.; Schulz, J.; Bingham, J. P.; Sweedler, J. V.

In: Journal of Experimental Biology, Vol. 214, No. 1, 01.01.2011, p. 147-161.

Research output: Contribution to journalArticle

Gilly, WF, Richmond, TA, Duda, TF, Elliger, C, Lebaric, Z, Schulz, J, Bingham, JP & Sweedler, JV 2011, 'A diverse family of novel peptide toxins from an unusual cone snail, Conus californicus', Journal of Experimental Biology, vol. 214, no. 1, pp. 147-161. https://doi.org/10.1242/jeb.046086
Gilly, W. F. ; Richmond, T. A. ; Duda, T. F. ; Elliger, C. ; Lebaric, Z. ; Schulz, J. ; Bingham, J. P. ; Sweedler, J. V. / A diverse family of novel peptide toxins from an unusual cone snail, Conus californicus. In: Journal of Experimental Biology. 2011 ; Vol. 214, No. 1. pp. 147-161.
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