Department of Physiology, Graduate School of Medicine, Osaka University.
Graduate School of Frontier Bioscience, Osaka University.
Proc Jpn Acad Ser B Phys Biol Sci. 2019;95(3):111-135. doi: 10.2183/pjab.95.010.
The voltage sensor domain (VSD) has long been studied as a unique domain intrinsic to voltage-gated ion channels (VGICs). Within VGICs, the VSD is tightly coupled to the pore-gate domain (PGD) in diverse ways suitable for its specific function in each physiological context, including action potential generation, muscle contraction and relaxation, hormone and neurotransmitter secretion, and cardiac pacemaking. However, some VSD-containing proteins lack a PGD. Voltage-sensing phosphatase contains a cytoplasmic phosphoinositide phosphatase with similarity to phosphatase and tensin homolog (PTEN). H1, a voltage-gated proton channel, also lacks a PGD. Within H1, the VSD operates as a voltage sensor, gate, and pore for both proton sensing and permeation. H1 has a C-terminal coiled coil that mediates dimerization for cooperative gating. Recent progress in the structural biology of VGICs and VSD proteins provides insights into the principles of VSD coupling conserved among these proteins as well as the hierarchy of protein organization for voltage-evoked cell signaling.
电压传感器结构域（VSD）长期以来一直被视为电压门控离子通道（VGICs）所特有的独特结构域。在 VGICs 中，VSD 以多种方式与孔门控结构域（PGD）紧密偶联，这与其在每种生理环境中的特定功能相适应，包括动作电位产生、肌肉收缩和松弛、激素和神经递质分泌以及心脏起搏。然而，一些包含 VSD 的蛋白质缺乏 PGD。电压感应磷酸酶包含细胞质磷酸肌醇磷酸酶，与磷酸酶和张力蛋白同源物（PTEN）具有相似性。H1 是一种电压门控质子通道，也缺乏 PGD。在 H1 中，VSD 作为电压传感器、门和孔，用于质子感应和渗透。H1 具有 C 端卷曲螺旋，介导二聚体的协同门控。VGIC 和 VSD 蛋白结构生物学的最新进展为这些蛋白之间保守的 VSD 偶联原理以及电压诱发细胞信号转导的蛋白质组织层次结构提供了深入的了解。
