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Toxicon. 2014 Oct;89:45-54. doi: 10.1016/j.toxicon.2014.06.014. Epub 2014 Jul 2.

A family of excitatory peptide toxins from venomous crassispirine snails: using Constellation Pharmacology to assess bioactivity.

Author information

1
Department of Biology, University of Utah, 257 South 1400 East, Salt Lake City, UT 84112, USA. Electronic address: imperial@biology.utah.edu.
2
Marine Science Institute, University of the Philippines, Diliman, Quezon City 1101, Philippines.
3
Institute of Physiology, University of Kiel, Hermann-Rodewald-Straße 5, 24118 Kiel, Germany.
4
Department of Biology, University of Utah, 257 South 1400 East, Salt Lake City, UT 84112, USA.
5
A.N. Severtzov Institute of Ecology and Evolution, Russian Academy of Science, Moscow, 119071 Russia.

Abstract

The toxinology of the crassispirine snails, a major group of venomous marine gastropods within the superfamily Conoidea, is largely unknown. Here we define the first venom peptide superfamily, the P-like crassipeptides, and show that the organization of their gene sequences is similar to conotoxin precursors. We provide evidence that one peptide family within the P-like crassipeptide superfamily includes potassium-channel (K-channel) blockers, the κP-crassipeptides. Three of these peptides were chemically synthesized (cce9a, cce9b and iqi9a). Using conventional electrophysiology, cce9b was shown to be an antagonist of both a human Kv1.1 channel isoform (Shaker subfamily of voltage-gated K channels) and a Drosophila K-channel isoform. We assessed the bioactivity of these peptides in native mammalian dorsal root ganglion neurons in culture. We demonstrate that two of these crassipeptides, cce9a and cce9b, elicited an excitatory phenotype in a subset of small-diameter capsaicin-sensitive mouse DRG neurons that were also affected by κJ-conotoxin PlXIVA (pl14a), a blocker of Kv1.6 channels. Given the vast complexity of heteromeric K-channel isoforms, this study demonstrates that the crassispirine venoms are a potentially rich source for discovering novel peptides that can help to identify and characterize the diversity of K-channel subtypes expressed in native neurons and other cell types.

KEYWORDS:

Conotoxin; Crassipeptide; Crassispirine snails; Potassium channel; cce9a; cce9b

PMID:
24997406
PMCID:
PMC4134995
DOI:
10.1016/j.toxicon.2014.06.014
[Indexed for MEDLINE]
Free PMC Article

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