8.B.17 The Sea Anemone Peptide Toxin Class III (ShI) Family
Cnidaria (sea anemone, coral, jellyfish, and hydroid) toxins target voltage-gated sodium and potassium channels. The sodium channel toxin is a member of the Toxin-4 Superfamily. It binds specifically to the sodium channel (Nav), thereby delaying its inactivation during signal transduction. Thus it strongly stimulates mammalian cardiac muscle contraction.These toxins are reviewed by Moran et al., 2009. Cnidarian toxin families, including peptide neurotoxins (voltage-gated Na+ and K+ channel-targeting toxins: NaTxs and KTxs, respectively), pore-forming toxins (actinoporins, aerolysin-related toxins, and jellyfish toxins), and the newly discovered small cysteine-rich peptides (SCRiPs).
The Sea Anemone peptide type III neurotoxin, ShI (Fogh et al., 1990), 3-d structure known (1SHI-A).
Sh1 of Stoichactis helianthus (P19651)
Sea Anemone peptide neurotoxin Am-3; blocks Na channels. These neurotoxins modulate sodium channels, and structure and functional Aspects have been reviewed (Monastyrnaya et al. 2022).
Am-3 of Antheopsis maculata (P69928)
Anthopleurin-A, AP-A, a heart stimulant; binds voltage-gated Na+ channels (structure known) (Frazão et al. 2012).
AP-A of Anthopleura xanthogrammica (P01530)
Actitoxin-Avd1f; U-AITX-Avd1f; Av6; Neurotoxin 6 of 72 aas and 2 TMSs.
U-AITX of Anemonia viridis (sea anemone)
N.vectensis toxin 14 of 85 aas and 1 N-terminal TMS. It binds to site 3 of voltage-gated sodium channels and inhibits the inactivation process (Moran et al. 2008). It is highly active on DmNav1/TipE (Drosophila) and is only weakly active on rat Nav1.4-beta-1/SCN4A-SCN1B, or on human Nav1.5-beta-1/SCN5A-beta-1. This reveals high specificity for arthropod over mammalian channels (Moran et al. 2008). In vivo, when released into the medium, this recombinant toxin induces impaired swimming, paralysis and death of the crustacean A.nauplii within several hours (Moran et al. 2012) and causes paralysis of cherry shrimps immediately after injection at very low doses (Columbus-Shenkar et al. 2018). Its effect on zebrafish (D.rerio) larvae is also rapid, since it induces tail twitching accompanied by impaired swimming after 20 minutes and complete paralysis within 45 minutes (Moran et al. 2012). It has also been observed to cause death of zebrafish larvae within 1 hour (Sachkova et al. 2019).
Toxin 14 of Nematostella vectensis (Starlet sea anemone)
Delta-actitoxin-Ate Neurotoxin short toxin (III)of 72 aas and 1 N-terminal TMS.
Asctitoxin-Ate of Actinia tenebrosa
Delta-actitoxin-Avd2c of 61 aas and 1 N-terminal TMS.
Actitoxin-Avd2c of Anemonia viridis