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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.

References associated with 8.B.31 family:

Madio, B., S. Peigneur, Y.K.Y. Chin, B.R. Hamilton, S.T. Henriques, J.J. Smith, B. Cristofori-Armstrong, Z. Dekan, B.A. Boughton, P.F. Alewood, J. Tytgat, G.F. King, and E.A.B. Undheim. (2018). PHAB toxins: a unique family of predatory sea anemone toxins evolving via intra-gene concerted evolution defines a new peptide fold. Cell Mol Life Sci 75: 4511-4524. 30109357