Functionality of the voltage-gated proton channel truncated in S4
Functionality of the voltage-gated proton channel truncated in S4
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DOI：
10.1073/pnas.0911868107
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发表时间：
2010-02-02
影响因子：
11.1
通讯作者：
Okamura, Yasushi
中科院分区：
文献类型：
--
作者：
Sakata, Souhei;Kurokawa, Tatsuki;Okamura, Yasushi
电压传感器结构域（VSD）是电压门控离子通道和电压敏感磷酸酶中的关键模块。在结构上，VSD和最近发现的电压门控质子通道（Hv channels）电压传感器蛋白（VSOP）和Hv1都含有四个跨膜片段。Hv通道的第四个跨膜段（S4）含有三个周期性排列的丝氨酸（R1，R2，R3）。它仍然是未知的质子渗透或电压传感如何耦合到离子渗透在HV通道。在这里，我们报告说，HV通道截断下游的R2在S4段保留大多数通道特性。两种测定，使用马来酰亚胺试剂的可及性进行的定点半胱氨酸扫描（通过Western印迹法检测）和插入犬胰腺微粒体均显示S4插入膜中，即使其在R2和R3位置之间被截短。这些发现提供了重要的线索的分子机制，潜在的电压传感和质子渗透的Hv通道。
The voltage sensor domain (VSD) is the key module for voltage sensing in voltage-gated ion channels and voltage-sensing phosphatases. Structurally, both the VSD and the recently discovered voltage-gated proton channels (Hv channels) voltage sensor only protein (VSOP) and Hv1 contain four transmembrane segments. The fourth transmembrane segment (S4) of Hv channels contains three periodically aligned arginines (R1, R2, R3). It remains unknown where protons permeate or how voltage sensing is coupled to ion permeation in Hv channels. Here we report that Hv channels truncated just downstream of R2 in the S4 segment retain most channel properties. Two assays, site-directed cysteine-scanning using accessibility of maleimide-reagent as detected by Western blotting and insertion into dog pancreas microsomes, both showed that S4 inserts into the membrane, even if it is truncated between the R2 and R3 positions. These findings provide important clues to the molecular mechanism underlying voltage sensing and proton permeation in Hv channels.