Isolation and structural identification of a potassium ion channel Kv4.1 inhibitor SsTx-P2 from centipede venom

• Published in: Zhejiang da xue xue bao. Journal of Zhejiang University. Medical sciences. Yi xue ban p. 1
• Main Authors: DU, Canwei, Yuan, Fuchu, Duan, Xinyi, Rong, Mingqiang, Meng, Er, Liu, Changjun
• Format: Journal Article
• Language: English
• Published: China 25-01-2024
• Subjects: Peptide SsTx-P2; Centipede venom; Kv4.1 channel; Inhibitor; Structure
• ISSN: 1008-9292

To isolate potassium ion channel Kv4.1 inhibitor from centipede venom, and to determine its primary and spatial structure.
Ion-exchange chromatography and reversed-phase high-performance liquid chromatography were performed to separate and purify peptide components of centipede venom, and their inhibiting effect on Kv4.1 channel was determined by whole-cell patch clamp recording. The molecular weight of isolated peptide Kv4.1 channel inhibitor was identified with MALDI-TOF, its primary sequence was determined by Edman degradation sequencing and two-dimensional mass spectrometry, its patial structure was established based on iterative thread assembly refinement online analysis.
A peptide SsTx-P2 was separated from centipede venom with the molecular weight of 6122.8, and its primary sequence consists of 53 amino acid residues, showed as NH
-ELTWDFVRTCCKLFPDKSECTKACATEFTGGDESRLKDVWPRKLRSGDSRLKD-OH. Peptide SsTx-P2 potently inhibited the current of Kv4.1 channel transiently transfected in HEK293 cell, with 1.0 μmol/L SsTx-P2 suppressing 95% current of Kv4.1 channel. Its spatial structure showed that SsTx-P2 shared a conserved helical structure.
The study has isolated a novel peptide SsTx-P2 from centipede venom, which can potently inhibit the potassium ion channel Kv4.1, and its spatial structure displays a certain degree of conservation.