PROSITE documentation PDOC60026

Ergtoxin (ErgTx) family signature

The Ergtoxin (ErgTx) family is a class of peptides from scorpion venom that specifically block ERG (ether-a-go-go-related gene) K+ channels of the nerve, heart and endocrine cells [1,2,3].

Peptides of the ErgTx family have from 42 to 47 amino acid residues cross-linked by four disulfide bridges. The four disulfide bridges have been assigned as C1-C4, C2-C6, C3-C7 and C5-C8 (see the schematic representation below) [1]. ErgTxs consist of a triple-stranded β-sheet and an α-helix (see <PDB:1NE5>), as is typical of K+ channel scorpion toxins. There is a large hydrophobic patch on the surface of the toxin, surrounding a central lysine residue located near the β-hairpin loop between the second and third strands of the β-sheet. It has been postulated that this hydrophobic patch is likely to form part of the binding surface of the toxin [2]. Peptides of the ErgTx family possess a Knottin scaffold (see <PDOC60004>) [E1].

                                        +------------+
                                        #            #
                        CxxxxCxxxxxCxxxCCxxxCxxxCxxxxC
                        |    |     |   |    |   |
                        |    |     +---|----|---+
                        |    +---------|----+
                        +--------------+

'C': conserved cysteine involved in a disulfide bond.
'#': positions of the cysteine, which are not involved in knottin scaffold.

Some proteins known to belong to the ErgTx family are listed below:

• ErgTx1, ErgTx2 and ErgTx3 from Centruroides elegans (Bark scorpion).
• ErgTx1, ErgTx2, ErgTx3 and ErgTx4 from Centruroides exilicauda (Bark scorpion).
• ErgTx1, ErgTx2 and ErgTx3 from Centruroides gracilis (Slenderbrown scorpion) (Florida bark scorpion).
• ErgTx1, ErgTx2, ErgTx3 and ErgTx4 from Centruroides limpidus limpidus (Mexican scorpion).
• ErgTx1, ErgTx2, ErgTx3, ErgTx4, ErgTx5 and γ-KTx 4.12 from Centruroides sculpturatus (Bark scorpion).
• ErgTx, ErgTx2, ErgTx3, ErgTx4 and ErgTx5 from Centruroides noxius (Mexican scorpion).

We have developed a pattern that contains the eight conserved cysteines.