Molecular Physiology & Biophysics, Faculty of Medicine/Graduate School of Medicine, Kagawa University, Miki-cho, Kagawa, Japan.
Adv Exp Med Biol. 2024;1461:109-125. doi: 10.1007/978-981-97-4584-5_8.
Voltage-gated proton channel (Hv) has activity of proton transport following electrochemical gradient of proton. Hv is expressed in neutrophils and macrophages of which functions are physiologically temperature-sensitive. Hv is also expressed in human sperm cells and regulates their locomotion. H transport through Hv is both regulated by membrane potential and pH difference across biological membrane. It is also reported that properties of Hv such as proton conductance and gating are highly temperature-dependent. Hv consists of the N-terminal cytoplasmic domain, the voltage sensor domain (VSD), and the C-terminal coiled-coil domain, and H permeates through VSD voltage-dependently. The functional unit of Hv is a dimer via the interaction between C-terminal coiled-coils assembly domain. We have reported that the coiled-coil domain of Hv has the nature of dissociation around our bodily temperature and mutational change of the coiled-coil affected temperature-sensitive gating, especially its temperature threshold. The temperature-sensitive gating is assessed from two separate points: temperature threshold and temperature dependence. In this chapter, I describe physiological roles and molecular structure mechanisms of Hv by mainly focusing on thermosensitive properties.
电压门控质子通道（Hv）具有顺着质子电化学梯度进行质子转运的活性。Hv 表达于中性粒细胞和巨噬细胞中，其功能对生理温度敏感。Hv 也表达于人精子细胞中，并调节其运动。Hv 通过质子通道的转运既受膜电位的调节，也受生物膜两侧 pH 差的调节。据报道，Hv 的质子电导和门控等特性高度依赖于温度。Hv 由 N 端胞质结构域、电压传感器结构域（VSD）和 C 端卷曲螺旋结构域组成，质子通过 VSD 电压依赖性地渗透。通过 C 端卷曲螺旋组装结构域的相互作用，Hv 的功能单位是二聚体。我们已经报道，Hv 的卷曲螺旋结构域在我们的体温周围具有解离的性质，卷曲螺旋的突变改变了温度敏感的门控，特别是其温度阈值。温度敏感性门控可以从两个独立的方面进行评估：温度阈值和温度依赖性。在本章中，我主要关注温度敏感特性，描述了 Hv 的生理作用和分子结构机制。
