近日，美国华盛顿大学William A. Catterall和Ning Zheng研究组解析了钠离子门控通道的静息态结构及其门控机制。 这一研究成果于2019年8月9日发表在国际学术期刊《细胞》上。

为了稳定静息构象，研究人员插入了改变电压的突变并在细菌钠离子通道Na VAb的电压传感器（VS）中引入一个二硫键交联。研究人员揭示了钠离子通道静息态的冷冻电镜结构以及完整的电压依赖门控机制。VS的S4区段处在细胞内，并与三个门控电荷通过跨膜电场。该运动形成连接S4到S4-S5连接器的弯头，从而收紧S6激活门周围的环，并防止其打开。 基于这一钠离子通道蛋白的高分辨率结构，这些发现支持经典的“滑动螺旋”电压感知机制，并为电压传感器功能、通道开启和活化门闭合提供了完整的门控机制。

研究人员表示，电压门控钠离子（Na V）通道在神经、肌肉和其他电兴奋细胞中启动动作电位。电压门控的结构基础是不清楚的，因为静息态仅存在于深度负电极膜电位时。

附：英文原文

Title: Resting-State Structure and Gating Mechanism of a Voltage-Gated Sodium Channel

Author: Goragot Wisedchaisri, Lige Tonggu, Eedann McCord, Tamer M. Gamal El-Din, Liguo Wang, Ning Zheng, William A. Catterall

Issue&Volume: Volume 178 Issue 4

Abstract: Voltage-gated sodium (Na V) channels initiate action potentials in nerve, muscle, and other electrically excitable cells. The structural basis of voltage gating is uncertain because the resting state exists only at deeply negative membrane potentials. To stabilize the resting conformation, we inserted voltage-shifting mutations and introduced a disulfide crosslink in the VS of the ancestral bacterial sodium channel Na VAb. Here, we present a cryo-EM structure of the resting state and a complete voltage-dependent gating mechanism. The S4 segment of the VS is drawn intracellularly, with three gating charges passing through the transmembrane electric field. This movement forms an elbow connecting S4 to the S4-S5 linker, tightens the collar around the S6 activation gate, and prevents its opening. Our structure supports the classical “sliding helix” mechanism of voltage sensing and provides a complete gating mechanism for voltage sensor function, pore opening, and activation-gate closure based on high-resolution structures of a single sodium channel protein.

DOI: https://doi.org/10.1016/j.cell.2019.06.031

Source: https://www.cell.com/cell/fulltext/S0092-8674(19)30734-2