Structural and Functional Characterization of the Heterodimeric Voltage-Gated Sodium Channel in the Green Peach Aphid Myzus persicae.

Voltage-gated sodium channels (VGSCs) are primary targets of pyrethroid insecticides, yet aphids possess a unique architecture with gene fission and a noncanonical DENS selectivity filter. Here, the VGSC of Myzus persicae was characterized using heterologous expression, electrophysiology, structural modeling, and molecular docking. Individual channel fragments failed to produce sodium currents, whereas linker concatenation partially restored activity with reduced amplitude, indicating impaired interdomain coupling. Despite the DENS motif, sodium selectivity was retained, indicating that ion discrimination can be maintained despite alterations in the canonical selectivity filter sequence. Molecular docking predicted genotype-dependent differences in pyrethroid binding modes among variants carrying mutations at positions 918 and 1014, suggesting potential effects on the local binding environment. These findings reveal an evolutionarily distinct functional organization of aphid VGSCs and provide a framework for future investigations into their interactions with pyrethroid insecticides.