Journal article
PHAB toxins: A unique family of predatory sea anemone toxins evolving via intra-gene concerted evolution defines a new peptide fold
Cellular and Molecular Life Sciences, Vol.75, pp.4511-4524
2018
Abstract
Sea anemone venoms have long been recognized as a rich source of peptides with interesting pharmacological and structural properties, but they still contain many uncharacterized bioactive compounds. Here we report the discovery, three-dimensional structure, activity, tissue localization, and putative function of a novel sea anemone peptide toxin that constitutes a new, sixth type of voltage-gated potassium channel (KV) toxin from sea anemones. Comprised of just 17 residues, κ-actitoxin-Ate1a (Ate1a) is the shortest sea anemone toxin reported to date, and it adopts a novel three-dimensional structure that we have named the Proline-Hinged Asymmetric β-hairpin (PHAB) fold. Mass spectrometry imaging and bioassays suggest that Ate1a serves a primarily predatory function by immobilising prey, and we show this is achieved through inhibition of Shaker-type KV channels. Ate1a is encoded as a multi-domain precursor protein that yields multiple identical mature peptides, which likely evolved by multiple domain duplication events in an actinioidean ancestor. Despite this ancient evolutionary history, the PHAB-encoding gene family exhibits remarkable sequence conservation in the mature peptide domains. We demonstrate that this conservation is likely due to intra-gene concerted evolution, which has to our knowledge not previously been reported for toxin genes. We propose that the concerted evolution of toxin domains provides a hitherto unrecognised way to circumvent the effects of the costly evolutionary arms race considered to drive toxin gene evolution by ensuring efficient secretion of ecologically important predatory toxins.
Details
- Title
- PHAB toxins: A unique family of predatory sea anemone toxins evolving via intra-gene concerted evolution defines a new peptide fold
- Authors/Creators
- B. Madio (Author/Creator) - The University of QueenslandS. Peigneur (Author/Creator) - KU LeuvenY.K.Y. Chin (Author/Creator) - The University of QueenslandB.R. Hamilton (Author/Creator) - The University of QueenslandS.T. Henriques (Author/Creator) - The University of QueenslandJ.J. Smith (Author/Creator) - The University of QueenslandB. Cristofori-Armstrong (Author/Creator) - The University of QueenslandZ. Dekan (Author/Creator) - The University of QueenslandB.A. Boughton (Author/Creator) - The University of MelbourneP.F. Alewood (Author/Creator) - The University of QueenslandJ. Tytgat (Author/Creator) - KU LeuvenG.F. King (Author/Creator) - The University of QueenslandE.A.B. Undheim (Author/Creator) - The University of Queensland
- Publication Details
- Cellular and Molecular Life Sciences, Vol.75, pp.4511-4524
- Publisher
- Springer
- Identifiers
- 991005544653007891
- Murdoch Affiliation
- Murdoch University
- Language
- English
- Resource Type
- Journal article
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- Citation topics
- 3 Agriculture, Environment & Ecology
- 3.274 Animal Sensing
- 3.274.2008 Cnidarian Biology
- Web Of Science research areas
- Biochemistry & Molecular Biology
- Cell Biology
- ESI research areas
- Molecular Biology & Genetics