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

Imperial, Julita S., Cabang, April B., Song, Jie, Raghuraman, Shrinivasan, Gajewiak, Joanna, Watkins, Maren, Showers-Corneli, Patrice, Fedosov, Alexander, Concepcion, Gisela P., Terlau, Heinrich, Teichert, Russell W. and Olivera, Baldomero M. (2014) A family of excitatory peptide toxins from venomous crassispirine snails: Using Constellation Pharmacology to assess bioactivity Toxicon, 89 . pp. 45-54.

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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 kappa P-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 K(v)1.1 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 kappa J-conotoxin PlXIVA (pl14a), a blocker of K(v)1.6 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. Published by Elsevier Ltd.

Document Type: Article
Additional Information: Times Cited: 0 0
Research affiliation: Kiel University > Kiel Marine Science
OceanRep > The Future Ocean - Cluster of Excellence
Refereed: Yes
ISSN: 0041-0101
Projects: Future Ocean
Date Deposited: 30 Mar 2015 12:26
Last Modified: 01 Feb 2018 11:23
URI: http://eprints.uni-kiel.de/id/eprint/27731

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