6AZA

NMR structure of sea anemone toxin Kappa-actitoxin-Ate1a

Summary for 6AZA

• Entry DOI: 10.2210/pdb6aza/pdb
• NMR Information: BMRB: 30342
• Descriptor: ARG-CYS-LYS-THR-CYS-SER-LYS-GLY-ARG-CYS-ARG-PRO-LYS-PRO-ASN-CYS-GLY-NH2 (1 entity in total)
• Functional Keywords: sea anemone; actinia tenebrosa; neurotoxin; ion channels, toxin
• Biological source: Actinia tenebrosa
• Total number of polymer chains: 1
• Total formula weight: 1898.33

Authors

Chin, Y.K.-Y.,Madio, B.,King, G.F.,Undheim, E.A.B. (deposition date: 2017-09-10, release date: 2018-09-12, Last modification date: 2023-06-14)

Primary citation

Madio, B.,Peigneur, S.,Chin, Y.K.Y.,Hamilton, B.R.,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.
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, 2018

PubMed 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 (K) 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 K 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.

PubMed: 30109357
DOI: 10.1007/s00018-018-2897-6

Experimental method

SOLUTION NMR