Structure of a eukaryotic voltage-gated sodium channel at near-atomic resolution
Structure of a eukaryotic voltage-gated sodium channel at near-atomic resolution
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DOI：
10.1126/science.aal4326
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发表时间：
2017-03-03
期刊：
影响因子：
56.9
通讯作者：
Yan, Nieng
中科院分区：
文献类型：
--
作者：
Shen, Huaizong;Zhou, Qiang;Yan, Nieng
电压门控钠（Nav）通道负责动作电位的起始和传播。它们与各种通道病有关，并被多种药物和天然毒素靶向。在这里，我们报告的低温电子显微镜结构的一个假定的NAV通道从美洲大蠊（指定NavPaS）在3.8埃的分辨率。四个重复序列的电压敏感结构域（VSD）表现出不同的构象。不对称选择性过滤前庭的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，保守的氨基末端结构域位于VSDI下方，羧基末端结构域与III-IV接头结合。NavPaS的结构为理解Nav及其相关电压门控钙通道的功能和疾病机制奠定了重要基础。
Voltage-gated sodium (Nav) 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 Nav channel from American cockroach (designated NavPaS) 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 VSDI, and a carboxy-terminal domain binds to the III-IV linker. The structure of NavPaS establishes an important foundation for understanding function and disease mechanism of Nav and related voltage-gated calcium channels.