Voltage-gated sodium (Na_v) channels initiate and propagate action potentials. Here, we present the cryo-EM structure of EeNa_v1.4, the Na_v channel from electric eel, in complex with the β1 subunit at 4.0 Å resolution. The immunoglobulin domain of β1 docks onto the extracellular L5_I and L6_IV loops of EeNa_v1.4 via extensive polar interactions, and the single transmembrane helix interacts with the third voltage-sensing domain (VSD_III). The VSDs exhibit "up" conformations, while the intracellular gate of the pore domain is kept open by a digitonin-like molecule. Structural comparison with closed Na_vPaS shows that the outward transfer of gating charges is coupled to the iris-like pore domain dilation through intricate force transmissions involving multiple channel segments. The IFM fast inactivation motif on the III-IV linker is plugged into the corner enclosed by the outer S4-S5 and inner S6 segments in repeats III and IV, suggesting a potential allosteric blocking mechanism for fast inactivation.

中文翻译：

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鳗鱼Nav1.4-β1配合物的结构。

电压门控钠（Na _v）通道启动并传播动作电位。在这里，我们介绍了EeNa _v 1.4（来自鳗鱼的Na _v通道）的低温-EM结构，其与β1亚基在4.0Å分辨率下复合。β1的免疫球蛋白结构域通过广泛的极性相互作用，停靠在EeNa _v 1.4的细胞外L5 _I和L6 _IV环上，并且单个跨膜螺旋与第三电压感测结构域（VSD _III）相互作用。VSD表现出“向上”构象，而孔结构域的细胞内门则被洋地黄素样分子保持打开状态。封闭Na _v的结构比较PaS显示门控电荷的向外转移通过涉及多个通道段的复杂力传递而耦合到虹膜状孔域扩张。III-IV接头上的IFM快速灭活基序插入重复III和IV中由外部S4-S5和内部S6片段围成的角落，表明了潜在的构象阻断机制，可实现快速灭活。