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

详细信息    查看全文

• 作者：Xueli Wang ; Bin Gao ; Shunyi Zhu ; ^{Zhusy@ioz.ac.cn" class="auth_mail" title="E-mail the corresponding author} ;
• 关键词：MeuTXKα3 ; K+ channel toxin ; Antibacterial peptide ; Mesobuthus eupeus ; Scorpion venom
• 刊名：Comparative Biochemistry and Physiology, Part C
• 出版年：2016
• 出版时间：January 2016
• 年：2016
• 卷：179
• 期：Complete
• 页码：72-78
• 全文大小：1054 K

文摘

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 (rK_v1.1–rK_v1.3) 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 rK_v1.2 and rK_v1.3 but a decreased activity on the Shaker channel without changing the potency on rK_v1.1, 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 52.01 μM 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.