Trp: a conserved aromatic residue crucial to the interaction of a scorpion peptide with sodium channels

• Published in: Journal of biochemistry (Tokyo) Vol. 168; no. 6; pp. 633 - 641
• Main Authors: Xu, Yijia, Sun, Jianfang, Yu, Yue, Kong, Xiaohua, Meng, Xiangxue, Liu, Yanfeng, Cui, Yong, Su, Yang, Zhao, Mingyi, Zhang, Jinghai
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 26.12.2020
• Subjects: Nav1.7; analgesic activity; AGAP; voltage-gated sodium channel; scorpion toxin
• ISSN: 0021-924X; 1756-2651
• DOI: 10.1093/jb/mvaa088

Abstract Anti-tumour-analgesic peptide (AGAP), one scorpion toxin purified from Buthus martensii Karsch, was known as its analgesic and anti-tumour activities. Trp38, a conserved aromatic residue of AGAP, might play important roles in its interaction with sodium channels. In this study, a mutant W38F was generated and effects of W38F were examined on hNav1.4, hNav1.5 and hNav1.7 by using whole-cell patch-clamp, which were closely associated to the biotoxicity of skeletal and cardiac muscles and pain signalling. The data showed that W38F decreased the inhibition effects of peak currents of hNav1.7, hNav1.4 and hNav1.5 compared with AGAP, notably, W38F reduced the analgesic activity compared with AGAP. The results suggested that Trp38 be a crucial amino acid involved in the interaction with these three sodium channels. The decreased analgesic activity of W38F might result from its much less inhibition of hNav1.7. These findings provided more information about the relationship between structure and function of AGAP and may facilitate the modification of other scorpion toxins with pharmacological effects. Graphical Abstract