title: A single-point mutation enhances dual functionality of a scorpion toxin.
abstract: Scorpion venom represents a tremendous, hitherto partially explored peptide library that has been proven to be useful not only for understanding ion channels but also for drug design. MeuTXKα3 is a functionally unknown scorpion toxin-like peptide. Here we describe new transcripts of this gene arising from alternative polyadenylation and its biological function as well as a mutant with a single-point substitution at site 30. Native-like MeuTXKα3 and its mutant were produced in Escherichia coli and their toxic function against Drosophila Shaker K(+) channel and its mammalian counterparts (rKv1.1-rKv1.3) were assayed by two-electrode voltage clamp technique. The results show that MeuTXKα3 is a weak toxin with a wide-spectrum of activity on both Drosophila and mammalian K(+) channels. The substitution of a proline at site 30 by an asparagine, an evolutionarily conserved functional residue in the scorpion α-KTx family, led to an increased activity on rKv1.2 and rKv1.3 but a decreased activity on the Shaker channel without changing the potency on rKv1.1, suggesting a key role of this site in species selectivity of scorpion toxins. MeuTXKα3 was also active on a variety of bacteria with lethal concentrations ranging from 4.66 to 52.01μM and the mutant even had stronger activity on some of these bacterial species. To the best of our knowledge, this is the first report on a bi-functional short-chain peptide in the lesser Asian scorpion venom. Further extensive mutations of MeuTXKα3 at site 30 could help improve its K(+) channel-blocking and antibacterial functions.
authors.affiliation: Group of Peptide Biology and Evolution, State Key Laboratory of Integrated Management of Pest Insects & Rodents, Institute of Zoology, Chinese Academy of Sciences, 1 Beichen West Road, Chaoyang District, 100101 Beijing, China.
authors.forename: Xueli
authors.initials: X
authors.lastname: Wang
authors.affiliation: Group of Peptide Biology and Evolution, State Key Laboratory of Integrated Management of Pest Insects & Rodents, Institute of Zoology, Chinese Academy of Sciences, 1 Beichen West Road, Chaoyang District, 100101 Beijing, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Gao
authors.affiliation: Group of Peptide Biology and Evolution, State Key Laboratory of Integrated Management of Pest Insects & Rodents, Institute of Zoology, Chinese Academy of Sciences, 1 Beichen West Road, Chaoyang District, 100101 Beijing, China. Electronic address: Zhusy@ioz.ac.cn.
authors.forename: Shunyi
authors.initials: S
authors.lastname: Zhu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D005260:Female; D008969:Molecular Sequence Data; D017354:Point Mutation / Q000235:genetics*; D026902:Potassium Channel Blockers / Q000737:chemistry / Q000302:isolation & purification; D017433:Protein Structure, Secondary; D012604:Scorpion Venoms / Q000737:chemistry / Q000235:genetics* / Q000302:isolation & purification*; D012605:Scorpions; D014982:Xenopus laevis
chemical_list: D026902:Potassium Channel Blockers; D012604:Scorpion Venoms
keywords: Antibacterial peptide; K(+) channel toxin; Mesobuthus eupeus; MeuTXKα3; Scorpion venom