Phospholipids and the origin of cationic gating charges in voltage sensors
Phospholipids and the origin of cationic gating charges in voltage sensors
复制标题
DOI：
10.1038/nature05416
复制
发表时间：
2006-12-07
期刊：
影响因子：
64.8
通讯作者：
MacKinnon, Roderick
中科院分区：
文献类型：
--
作者：
Schmidt, Daniel;Jiang, Qiu-Xing;MacKinnon, Roderick
细胞通过在细胞周围膜中发生的物理和化学过程与外部环境进行交流。膜作为一个屏障，也是一个特殊的环境，膜蛋白能够在其中进行重要的过程。某些膜蛋白具有检测膜电压和调节离子传导或酶活性的能力（1，2）。这种电压依赖性过程依赖于被称为电压传感器的蛋白质结构域的作用，这些蛋白质结构域嵌入细胞膜内并含有过量的带正电荷的氨基酸，这些氨基酸对电场起反应。薄膜如何创造适合电压传感器的环境？在这里，我们表明在各种条件下，电压依赖性K+通道的功能是依赖于带负电荷的磷脂分子的磷酸二酯。非电压依赖性K+通道不表现出相同的依赖性。这些数据使我们提出，磷脂膜，通过提供带正电荷的电压传感器精氨酸残基和带负电荷的脂质磷酸二酯基团之间的稳定的相互作用，提供了一个合适的环境，充满活力的稳定性和操作的电压传感机器。我们认为，精氨酸残基的电压传感器的使用是一种适应细胞膜的磷脂成分。
Cells communicate with their external environment through physical and chemical processes that take place in the cell-surrounding membrane. The membrane serves as a barrier as well as a special environment in which membrane proteins are able to carry out important processes. Certain membrane proteins have the ability to detect the membrane voltage and regulate ion conduction or enzyme activity(1,2). Such voltage-dependent processes rely on the action of protein domains known as voltage sensors, which are embedded inside the cell membrane and contain an excess of positively charged amino acids, which react to an electric field. How does the membrane create an environment suitable for voltage sensors? Here we show under a variety of conditions that the function of a voltage-dependent K+ channel is dependent on the negatively charged phosphodiester of phospholipid molecules. A non-voltage-dependent K+ channel does not exhibit the same dependence. The data lead us to propose that the phospholipid membrane, by providing stabilizing interactions between positively charged voltage-sensor arginine residues and negatively charged lipid phosphodiester groups, provides an appropriate environment for the energetic stability and operation of the voltage-sensing machinery. We suggest that the usage of arginine residues in voltage sensors is an adaptation to the phospholipid composition of cell membranes.