State Key Laboratory of Membrane Biology, Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences and School of Medicine, Tsinghua University, Beijing, China; Beijing Advanced Innovation Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing, China.
Beijing Advanced Innovation Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing, China.
Cell. 2017 Jul 27;170(3):470-482.e11. doi: 10.1016/j.cell.2017.06.039. Epub 2017 Jul 20.
Voltage-gated sodium (Na) channels initiate and propagate action potentials. Here, we present the cryo-EM structure of EeNa1.4, the Na 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 and L6 loops of EeNa1.4 via extensive polar interactions, and the single transmembrane helix interacts with the third voltage-sensing domain (VSD). 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 NaPaS 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.
电压门控钠离子 (Na) 通道启动并传播动作电位。在这里，我们展示了来自电鳗的 Na 通道 EeNa1.4 与 β1 亚基复合物的冷冻电镜结构，分辨率为 4.0 Å。β1 的免疫球蛋白结构域通过广泛的极性相互作用与 EeNa1.4 的细胞外环 L5 和 L6 环对接，而单一跨膜螺旋与第三电压感应结构域 (VSD) 相互作用。VSDs 呈现“向上”构象，而孔域的细胞内门则被类似于去污剂的分子保持打开状态。与封闭的 NaPaS 的结构比较表明，门控电荷的外向转移通过涉及多个通道片段的复杂力传递与虹膜状孔域扩张偶联。III-IV 连接上的 IFM 快速失活模体插入到 III 和 IV 重复的外 S4-S5 和内 S6 片段包围的角落中，提示快速失活的潜在变构阻断机制。
