PHAB toxins: a unique family of predatory sea anemone toxins evolving via intra-gene concerted evolution defines a new peptide fold

Madio, B.; Peigneur, S.; Chin, Y.K.Y.; Hamilton, B.; Henriques, S.T.; Smith, J.J.; Cristofori-Armstrong, B.; Dekan, Z.; Boughton, B.A.; Alewood, P.F.; Tytgat, J.; King, G.F.; Undheim, E.A.B.

doi:/10.1007/s00018-018-2897-6

www.marinebiotech.eu/

log in

[ report an error in this record ]

basket (0): add | show

PHAB toxins: a unique family of predatory sea anemone toxins evolving via intra-gene concerted evolution defines a new peptide fold

Madio, B.; Peigneur, S.; Chin, Y.K.Y.; Hamilton, B.; Henriques, S.T.; Smith, J.J.; Cristofori-Armstrong, B.; Dekan, Z.; Boughton, B.A.; Alewood, P.F.; Tytgat, J.; King, G.F.; Undheim, E.A.B. (2018). 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 75(24): 4511-4524. https://dx.doi.org/10.1007/s00018-018-2897-6

In: Cellular and molecular life sciences. ISSN 1420-682X; e-ISSN 1420-9071

Available in	Authors
VLIZ: Open Marine Archive 328400 [ download pdf ]

Keyword

Marine/Coastal

Author keywords

Neurotoxin; Ion channel; Mass spectrometry imaging; 3D structure;Concerted evolution; Extreme resolution mass spectrometry imaging;On-tissue reduction alkylation

Authors		Top
Madio, B. Peigneur, S., more Chin, Y.K.Y. Hamilton, B. Henriques, S.T.	Smith, J.J. Cristofori-Armstrong, B. Dekan, Z. Boughton, B.A.	Alewood, P.F. Tytgat, J., more King, G.F. Undheim, E.A.B.

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.

All data in the Integrated Marine Information System (IMIS) is subject to the VLIZ privacy policy

Top | Authors