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.



This family belongs to the The Toxin/Amyloid/Protease Inhibitor (TAPI) Superfamily.

 

References:

Castaneda O. and Harvey AL. (2009). Discovery and characterization of cnidarian peptide toxins that affect neuronal potassium ion channels. Toxicon. 54(8):1119-24.

Examples:

TC#NameOrganismal TypeExample
8.B.13.1.1Kalicludine 3 toxin (59 aas) There are three types, AsKCl-3, which block Kv1.2 K+ channels. Shows 48% identity (e-11) with a central region of an Alzheimer's disease amyloid A4 homologue (1.C.50.1.1).

Sea anemones

Kalicludine 3 of Anemonia sulcata (Q9TWF8)

 
8.B.13.1.2

Tabserpin of 76 aas and 1 TMS. It is a werine-type endopeptidase inhibitor.

Tabserpin of Tabanus yao (Horsefly)

 
8.B.13.1.3

Pancreatic trypsin inhibitor-like isoform X1 of 123 aas and 1 TM

Trypsin inhibitor of Bubalus bubalis (water buffalo)

 
8.B.13.1.4

Kunitz/BPTI-like toxin of 84 aa

Toxin of Notechis scutatus (mainland tiger snake)

 
Examples:

TC#NameOrganismal TypeExample
8.B.13.2.1

Kunitz-type protease inhibitor 2 of 383 aas and 2 TMSs, N- and C-terminal. It is a member of the Kunitz_BAI (KU) Superfamily.

KU of Salvelinus alpinus (Arctic char)

 
8.B.13.2.2

Kunitz-type protease inhibitor 1-like isoform X1 of 528 aas and 2 TMSs, N- and C-terminal. It seems to have three internal repeats, the first two of about 134 aas, and the third shorter; the first starts at about residue 116, the second at about residue 257, and the third at about residue 391. The same regions are homologous to the shorter members of this superfamily (the proteolytically processed amyloid proteins, toxins and inhibitors, including thise with TC# 8.B.13.1.1 and 1.C.50.1.1.

KU of Oncorhynchus kisutch (coho salmon)