1. 德国小蠊钠离子通道 V295N 突变对 α-蝎毒素 LqhαIT 敏感性的影响.
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温淑璇, 马 媛, 陆容材, 耿俊杰, 张 坤, and 吴少英
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SODIUM channels , *BLATTELLA germanica , *ACTION potentials , *AMERICAN cockroach , *AMINO acid sequence , *MOLECULAR docking - Abstract
Voltage-gated sodium channels (VGSCs) are essential in cell electrical signal transmission, which controls the initiation and propagation of action potentials between neurons and other excitable cells, and rapid inactivation of sodium channels is critical for electrical signalling. Scorpion toxins act on sodium channels and affect the rapid deactivation rate of the channels. Therefore, it is of great importance to analyze the interaction mechanism between scorpion toxins and sodium channels. By comparing the amino acid sequences of Blattella germanica, Periplaneta americana and mammalian sodium channels, it was found that four different amino acids found are I291L, Y292F, V295N, and L406I. Site-directed mutation technique was used to construct four amino acid mutant plasmids on the B. germanica VGSCs, and Xenopus oocytes were employed as vehicles for gene expression. Electrophysiological results showed that the V295N mutation significantly reduced the sensitivity of the sodium channel to α-scorpion toxin Lqh IT (approximately 21.63 - fold). Further 3D homology modeling and molecular docking of the scorpion toxin revealed that the V295N mutation discovered sodium channel M291 to form a hydrogen bond with the K63 amino acid of LqhαIT, which prevented its binding with LqhαIT. In conclusion, V295N mutation indirectly affected the binding of the channel to LqhαIT, resulting in a reduction in the sensitivity of the channel to LqhαIT. [ABSTRACT FROM AUTHOR]
- Published
- 2025
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