8.B.13 The Sea Anemone Peptide Toxin Class 2 (Kalicludine) Family
Peptides have been isolated from several species of sea anemones and shown to block currents through various potassium ion channels, particularly in excitable cells. The toxins can be grouped into four structural classes: type 1 with 35-37 amino acid residues and three disulphide bridges; type 2 with 58-59 residues and three disulphide bridges; type 3 with 41-42 residues and three disulphide bridges; and type 4 with 28 residues and two disulphide bridges (Castañeda & Harvey, 2009). Examples from the first class are BgK from Bunodosoma granulifera, ShK from Stichodactyla helianthus and AsKS (or kaliseptine) from Anemonia sulcata (now A. viridis). These interfere with binding of radiolabelled dendrotoxin to synaptosomal membranes and block currents through channels with various Kv1 subunits and also intermediate conductance K(Ca) channels. Toxins in the second class are homologous to Kunitz-type inhibitors of serine proteases; these toxins include kalicludines (AsKC 1-3) from A. sulcata and SHTXIII from S. haddoni; they block Kv1.2 channels. The third structural group (8.B.11) includes proteins from A. sulcata and Anthropleura elegantissima. Their pharmacological specificities differs: BDS-I and -II toxins block currents involving Kv3 subunits while APETx1 blocks ERG channels. The fourth group comprises the SHTX I and II toxins from S. haddoni. Their channel blocking specificity is not yet known, but they displace dendrotoxin binding from synaptosomal membranes (Castañeda & Harvey, 2009). These small toxins (e.g., 8.B.13.1.1) are homologous throughout their lengths to a central part of amyloid-β protein precursors such as the one under TC# 1.C.50.1.2.