Voltage sensor ring in a native structure of a membrane-embedded potassium channel.
Voltage sensor ring in a native structure of a membrane-embedded potassium channel.
复制标题
膜嵌入钾通道天然结构中的电压传感器环。
DOI：
10.1073/pnas.1218203110
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发表时间：
2013
影响因子：
11.1
通讯作者：
Jiang,Qiu-Xing
中科院分区：
文献类型：
--
作者：
Shi,Liang;Zheng,Hongjin;Zheng,Hui;Borkowski,BrianA;Shi,Dan;Gonen,Tamir;Jiang,Qiu-Xing
电压门控离子通道支持细胞中的电化学活性，并在很大程度上负责整个神经系统的信息流。这些通道中的电压传感器域感测跨膜电位的变化并控制跨膜的离子通量。洗涤剂中的一些电压门控离子通道的X射线结构已经确定，并揭示了其各自的电压传感器域之间的明确的结构变化。最近的研究表明，电压门控通道周围的脂质可以直接改变其在膜上的构象状态。由于这些差异，天然膜中电压传感的结构基础仍然难以捉摸。在这里，通过对膜包埋蛋白的电子晶体学分析，我们提出了电压门控钾通道在其失活状态下的详细视图。与所有已知的洗涤剂中电压门控离子通道的结构相反，我们的数据揭示了一种独特的构象，其中来自Aeropyrum pernix（KvAP）的电压门控钾通道的四个电压传感器结构域形成完全围绕通道的孔结构域的环状结构。这种结构被称为电压传感器环。我们的生物化学和电生理学研究支持电压传感器环代表生理构象。这些数据共同表明，脂质对通道结构产生强烈的影响，这些影响可能会改变膜破裂。我们的研究结果具有广泛的影响，脂质-蛋白质的相互作用，特别是电压传感的机制。
Voltage-gated ion channels support electrochemical activity in cells and are largely responsible for information flow throughout the nervous systems. The voltage sensor domains in these channels sense changes in transmembrane potential and control ion flux across membranes. The X-ray structures of a few voltage-gated ion channels in detergents have been determined and have revealed clear structural variations among their respective voltage sensor domains. More recent studies demonstrated that lipids around a voltage-gated channel could directly alter its conformational state in membrane. Because of these disparities, the structural basis for voltage sensing in native membranes remains elusive. Here, through electron-crystallographic analysis of membrane-embedded proteins, we present the detailed view of a voltage-gated potassium channel in its inactivated state. Contrary to all known structures of voltage-gated ion channels in detergents, our data revealed a unique conformation in which the four voltage sensor domains of a voltage-gated potassium channel fromAeropyrum pernix(KvAP) form a ring structure that completely surrounds the pore domain of the channel. Such a structure is named the voltage sensor ring. Our biochemical and electrophysiological studies support that the voltage sensor ring represents a physiological conformation. These data together suggest that lipids exert strong effects on the channel structure and that these effects may be changed upon membrane disruption. Our results have wide implications for lipid–protein interactions in general and for the mechanism of voltage sensing in particular.