8.B.31. The Shaker-like Peptide Inhibitor, Kappa-actitoxin-Ate1a, Ate1a) Family
Ate1a is a selective voltage-gated potassium channel inhibitor that is used for prey capture (Madio et al. 2018). It inhibits several potassium channels, but not all (Kv1.1/KCNA1 (IC50=353 nM), Kv1.2/KCNA2 (IC50=146 nM), Kv1.3/KCNA3 (IC50=3051 nM), Kv1.6/KCNA6 (IC50=191 nM), and Shaker IR (23% inhibition at 3 µM)) (Madio et al. 2018). In vivo, injection of this toxin into amphipods results in impaired swimming followed by contractile paralysis (Madio et al. 2018). They reported the discovery, three-dimensional structure, activity, tissue localization, and putative function of this sea anemone peptide toxin that constitutes a sixth type of voltage-gated potassium channel (KV) toxin from sea anemones. Ate1a adopts a novel three-dimensional structure that has been named the Proline-Hinged Asymmetric β-hairpin (PHAB) fold. Mass spectrometry imaging and bioassays suggested that Ate1a serves a primarily predatory function by immobilising prey. 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. Madio et al. 2018 demonstrated that this conservation is likely due to intra-gene concerted evolution. The concerted evolution of toxin domains may provide a 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.