State Key Laboratory of Membrane Biology, Tsinghua University, Beijing 100084, China.
Beijing Advanced Innovation Center for Structural Biology, Tsinghua University, Beijing 100084, China.
Science. 2017 Mar 3;355(6328). doi: 10.1126/science.aal4326. Epub 2017 Feb 9.
Voltage-gated sodium (Na) channels are responsible for the initiation and propagation of action potentials. They are associated with a variety of channelopathies and are targeted by multiple pharmaceutical drugs and natural toxins. Here, we report the cryogenic electron microscopy structure of a putative Na channel from American cockroach (designated NaPaS) at 3.8 angstrom resolution. The voltage-sensing domains (VSDs) of the four repeats exhibit distinct conformations. The entrance to the asymmetric selectivity filter vestibule is guarded by heavily glycosylated and disulfide bond-stabilized extracellular loops. On the cytoplasmic side, a conserved amino-terminal domain is placed below VSD, and a carboxy-terminal domain binds to the III-IV linker. The structure of NaPaS establishes an important foundation for understanding function and disease mechanism of Na and related voltage-gated calcium channels.
电压门控钠离子（Na）通道负责动作电位的产生和传播。它们与多种通道病有关，也是多种药物和天然毒素的作用靶点。在这里，我们报道了在 3.8 埃分辨率下来自美洲大蠊（命名为 NaPaS）的一种假定 Na 通道的低温电子显微镜结构。四个重复的电压感应结构域（VSD）呈现出不同的构象。非对称选择性滤过门入口由高度糖基化和二硫键稳定的细胞外环保护。在细胞质侧，一个保守的氨基末端结构域位于 VSD 下方，一个羧基末端结构域与 III-IV 连接子结合。NaPaS 的结构为理解 Na 和相关电压门控钙通道的功能和疾病机制奠定了重要基础。
