A Novel Scorpion Toxin LmKTx13 Inhibits the Voltage-gated Potassium Channel Kv1.3
10.13865/j.cnki.cjbmb.2025.09.1332
- VernacularTitle:一种新型蝎毒素LmKTx13抑制电压门控钾通道Kv1.3的活性研究
- Author:
Jia-Xin QIN
1
;
Xiao-Qing LUO
1
;
Min-Juan LU
1
;
Jun-Xian JU
1
;
Qing ZHOU
1
;
Wen-Xing WANG
1
;
Zhong-Hua LIU
1
;
Min-Zhi CHEN
1
;
Xi ZHOU
1
Author Information
1. 湖南师范大学生命科学学院动物多肽药物创制国家地方联合工程实验室,长沙 410081
- Publication Type:Journal Article
- Keywords:
voltage-gated potassium channel subtype 1.3(Kv1.3);
autoimmune diseases;
Lychas mu-cronatus;
LmKTx13;
scorpion toxin
- From:
Chinese Journal of Biochemistry and Molecular Biology
2025;41(10):1392-1401
- CountryChina
- Language:Chinese
-
Abstract:
Kv1.3,a voltage-gated potassium channel,is highly expressed in T lymphocytes,the nervous system,and vascular smooth muscle cells.It plays a critical role in membrane excitability and electrical signal transduction,serving as an important target for studying T-cell function and providing a promising direction for developing therapeutics against autoimmune and inflammatory diseases.Therefore,the de-velopment of specific inhibitors of Kv1.3 channel has emerged as a novel therapeutic strategy for these disorders.In this study,we isolated and purified a novel Kv1.3-inhibitory peptide toxin,LmKTx13,from the venom of the scorpion Lychas mucronatus using reversed-phase high-performance liquid chroma-tography(RP-HPLC).LmKTx13 consists of 38 amino acid residues,including six cysteines that form three disulfide bonds.Whole-cell patch-clamp recordings revealed that LmKTx13 potently inhibited Kv1.3 with an IC50 of 7.92±3.0 nmol/L.Selectivity analysis showed that 2 μmol/L LmKTx13 also in-hibited Kv1.2 and Kv1.7,but exhibited no significant effects on other potassium channel subtypes or voltage-gated sodium channels.Further investigation into the mechanism demonstrated that LmKTx13 acts as a pore-blocking inhibitor of Kv1.3.By analyzing the effects of LmKTx13 on Kv1.3 channel gating ki-netics and performing sequence alignment of the pore regions of Kv1.3 and Kv1.5,we constructed site-directed mutants and identified the pore region of Kv1.3 as the critical binding site for LmKTx13.Key residues involved in the interaction included T425,G427,and H451.In summary,we discovered a no-vel pore-blocking Kv1.3 inhibitor,LmKTx13,from L.mucronatus venom,which exhibits high affinity and selectivity for Kv1.3.These findings highlight its potential as a potential lead molecule for developing Kv1.3-targeted therapeutics.
