PROSITE documentation PDOC51862 [for PROSITE entry PS51862]

BetaSPN-type cysteine-stabilized alpha/beta (CS-alpha/beta) domain profile

Scorpion venoms are complex mixture of peptides with a variety of pharmacological functions. These toxin peptides include ion channel modulators, antibacterial peptides, and protease inhibitors. Scorpion toxins targeting various ion channels share a cysteine-stabilized α/β (CS-α/β) structure, which can be divided into two types: short-chain toxins of 23–42 amino acid residues with 3 or 4 disulfide bridges, which are commonly potassium channel blockers, and long-chain toxins of 53–78 amino acids, which are mostly modulators of sodium channels.

In addition to the classic short-chain toxins such as α-KTxs, which are specific for potassium channels, long-chain toxins with unique structure and function, which were named β-KTxs and scorpine-like peptides, were identified from the scorpion families Buthidae, Scorpionidae and Caraboctonidae. Peptides of the βSPN (β-KTxs and scorpines) family, which are 59–75 amino acid residues in length, display various antimicrobial, cytolytic, and potassium channel-blocking activities. βSPN family full-length mature peptides contain two structural domains that confer them bi-functionality: the amphipathic α-helical N-terminal domain has cytolytic or antimicrobial activity, while the three-disulfid bridged C-terminal domain with the consensus CS-α/β motif has K(+) channel blocking activity. Sequence analysis revealed that the βSPN family can be divided into three distinct groups: (1) β-KTx-like peptides from buthids; (2) Scorpine-like peptides from Scorpionidae and Caraboctonidae species, including scorpine, Opiscorpines 1–4, HgeScplp1, HgeScplp2 and Heteroscorpine 1; (3) heterogeneous peptides similar to BmTXKβ of buthids and iurids [1,2,3,4,5].

The βSPN-type CS-α/β domain is more closely related to invertebrate defensins, antimicrobial peptides involved in the innate immune response of several invertebrate groups (see <PDOC00356>), than to the classical scorpion toxins. Its structure shows an α helix along with one β sheet stabilized by three disulfide bridges, folding into a CS-α/β motif (see <PDB:5IPO>). The connectivity between the ordinal numbered cysteines is C1-C4, C2-C5, and C3-C6 [5].

The profile we developed covers the entire βSPN-type CS-α/β domain.