Fujiwara Yuichiro, Okamura Yasushi
Laboratory of Integrative Physiology, Graduate School of Medicine, Osaka University, Suita, Japan.
Curr Top Membr. 2014;74:259-92. doi: 10.1016/B978-0-12-800181-3.00010-5.
The voltage-gated proton channel (Hv) mediates robust proton transport down the proton electrochemical gradient. Hv is mainly expressed in immune cells, including neutrophils and macrophages, the physiological functions of which are temperature sensitive. In those cells, Hv plays key roles in the regulation of reactive oxygen species production and pH homeostasis. Proton transport through Hv is regulated by both the membrane potential and the pH difference across the cell membrane. Earlier studies showed that the properties of Hv, including proton conductance and gating, are highly temperature dependent. Hv consists of a voltage sensor domain involved in both voltage sensing and proton permeation and a C-terminal coiled coil region. Although the channel's activities are innate to the protomers, normally two protomers assemble as a dimer via interaction between C-terminal coiled coils. We recently discovered that the coiled-coil region of Hv dissociates at around room temperature, and that subtle changes in the coiled-coil region affect temperature-sensitive gating. In this chapter, we describe the physiological functions and molecular mechanisms of Hv, focusing mainly on the structure and thermosensitive properties of Hv.
电压门控质子通道（Hv）介导质子沿质子电化学梯度进行高效运输。Hv主要表达于免疫细胞，包括中性粒细胞和巨噬细胞，其生理功能对温度敏感。在这些细胞中，Hv在调节活性氧生成和pH稳态方面发挥关键作用。通过Hv的质子运输受膜电位和跨细胞膜的pH差异共同调节。早期研究表明，Hv的特性，包括质子电导和门控，高度依赖于温度。Hv由一个参与电压传感和质子通透的电压传感器结构域以及一个C端卷曲螺旋区域组成。尽管通道的活性是原聚体固有的，但通常两个原聚体通过C端卷曲螺旋之间的相互作用组装成二聚体。我们最近发现，Hv的卷曲螺旋区域在室温左右会解离，并且卷曲螺旋区域的细微变化会影响温度敏感型门控。在本章中，我们将描述Hv的生理功能和分子机制，主要聚焦于Hv的结构和热敏特性。
