Oral Presentation HUPO 2019 - 18th Human Proteome Organization World Congress

Thermostable potassium channel-inhibiting neurotoxins in processed scorpion medicinal material revealed by proteomic analysis: implications of its pharmaceutical basis in traditional Chinese medicine (#218)

Fan Yang 1 , Danya Wang 1 2 , Yongjia Tong 1 2 , Chenghu Qin 1 , Liuting Yang 1 2 , Fei Yu 1 2 , Xin Huang 1 , Shuang Liu 1 , Zhijian Cao 1 3 , Lin Guo 1 2 , Wenxin Li 1 3 , Yingliang Wu 1 3 , Xiaolu Zhao 1 2
  1. State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei, China
  2. Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, Hubei, China
  3. Center for BioDrug Research, Wuhan University, Wuhan, Hubei, China

The neurotoxins of venomous scorpion act on ion channels. Whether these neurotoxins are retained in processed Buthus martensii Karsch scorpions used in traditional Chinese medicine materials is unknown. Here, we performed a comprehensive mass spectrometry-based proteomic characterization of functionally active toxins in the processed medicinal scorpion material. Our proteomic analysis combining HCD and ETD techniques revealed 22 full-length and 44 truncated thermostable potassium channel-modulatory toxins that preserved six conserved cysteine residues capable of forming the three disulfide bonds necessary for toxicity. Additionally, a broad spectrum of degraded toxin fragments was found, indicating their relative thermal instability which enabled toxicity reduction. Furthermore, the suppression of IL-2 production in Jurkat cells and the reduced delayed-type hypersensitivity (DTH) response demonstrated that the extracts have immunoregulatory activity both in vitro and in vivo. Our work describes the first "map" of functionally active scorpion toxins in processed scorpion medicinal material, which is helpful to unveil the pharmaceutical basis of the processed scorpion medicinal material in traditional Chinese medicine.