A single-point mutation enhances dual functionality of a scorpion toxin

Area of Science:

• Biochemistry and Molecular Biology
• Pharmacology
• Toxinology

Background:

• Scorpion venom is a rich source of peptides with potential applications in drug design and understanding ion channel function.
• MeuTXKα3 is a novel scorpion toxin-like peptide with an unknown biological function.
• Alternative polyadenylation generates new transcripts for the MeuTXKα3 gene.

Purpose of the Study:

• To investigate the biological function of the scorpion toxin-like peptide MeuTXKα3.
• To characterize the activity of native-like MeuTXKα3 and a single-point mutant (Pro30Asn) against potassium channels and bacteria.
• To explore the role of residue 30 in the species selectivity and functional properties of scorpion toxins.

Main Methods:

• Production of native-like MeuTXKα3 and its Pro30Asn mutant in Escherichia coli.
• Assay of toxic function against Drosophila Shaker K(+) channel and mammalian Kv1.1-Kv1.3 channels using two-electrode voltage clamp.
• Determination of antibacterial activity and lethal concentrations against various bacterial species.

Main Results:

• MeuTXKα3 displays weak, wide-spectrum activity against both Drosophila and mammalian potassium channels.
• The Pro30Asn mutation enhances activity against rKv1.2 and rKv1.3 channels but reduces it against the Shaker channel, indicating a role in species selectivity.
• MeuTXKα3 exhibits significant antibacterial activity, with the mutant showing even stronger effects on some bacterial species, suggesting bifunctional properties.

Conclusions:

• MeuTXKα3 is a novel, bifunctional short-chain peptide found in lesser Asian scorpion venom, active against potassium channels and bacteria.
• The proline at site 30 is crucial for the species selectivity of MeuTXKα3 on potassium channels.
• Further studies involving mutations at site 30 could optimize the potassium channel-blocking and antibacterial potential of MeuTXKα3 for therapeutic applications.