X-ray crystal structure of voltage-gated proton channel
X-ray crystal structure of voltage-gated proton channel
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DOI：
10.1038/nsmb.2783
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发表时间：
2014-04-01
影响因子：
16.8
通讯作者：
Nakagawa, Atsushi
中科院分区：
文献类型：
--
作者：
Takeshita, Kohei;Sakata, Souhei;Nakagawa, Atsushi
电压门控质子通道Hv1(或VSOP)具有电压敏感区域(VSD)，具有电压传感和质子渗透的双重作用。它的门控对pH和锌离子很敏感。在这里，我们提出了3.45埃分辨率的静息态小鼠Hv1的晶体结构。该结构呈闭合伞形，由细胞质卷曲螺旋和电压敏感螺旋S4组成的长螺旋，并具有一个宽阔的内部可到达的前庭。S4的三个精氨酸中有两个位于构成门控电荷转移中心的苯丙氨酸下方。每个原核糖体的胞外区与一个锌离子配位，因此表明锌离子通过竞争酸性残基来稳定Hv1的休眠状态，否则这些酸性残基将与S4上的电压敏感正电荷形成盐桥。这些发现为理解电压传感和质子渗透的一般原理提供了平台。
The voltage-gated proton channel Hv1 (or VSOP) has a voltage-sensor domain (VSD) with dual roles of voltage sensing and proton permeation. Its gating is sensitive to pH and Zn2+. Here we present a crystal structure of mouse Hv1 in the resting state at 3.45-angstrom resolution. The structure showed a 'closed umbrella' shape with a long helix consisting of the cytoplasmic coiled coil and the voltage-sensing helix, S4, and featured a wide inner-accessible vestibule. Two out of three arginines in S4 were located below the phenylalanine constituting the gating charge-transfer center. The extracellular region of each protomer coordinated a Zn2+, thus suggesting that Zn2+ stabilizes the resting state of Hv1 by competing for acidic residues that otherwise form salt bridges with voltage-sensing positive charges on S4. These findings provide a platform for understanding the general principles of voltage sensing and proton permeation.