| Influence of the V295N mutation of the Blattella germanica sodium channel on the sensitivity of the α-scorpion toxin LqhαIT |
| Received:August 31, 2024 Revised:January 06, 2025 Download the full |
| DOI：10.16801/j.issn.1008-7303.2024.0114 |
| Key Words:Blattella germanica sodium channel LqhαIT site-directed mutagenesis two-electrode voltage clamp homologous modeling |
| Fund Project:Funding: Supported by the Project of Sanya Yazhou Bay Science |
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| Abstract: |
| Voltage-gated sodium channels(VGSC) 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 signaling. Scorpion toxins acting 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 LqhIT (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 itsbinding 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. |
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