Sato C, Ueno Y, Asai K, Takahashi K, Sato M, Engel A, Fujiyoshi Y
Supermolecular Science Division, Electrotechnical Laboratory, Tsukuba, Japan.
Nature. 2001 Feb 22;409(6823):1047-51. doi: 10.1038/35059098.
Voltage-sensitive membrane channels, the sodium channel, the potassium channel and the calcium channel operate together to amplify, transmit and generate electric pulses in higher forms of life. Sodium and calcium channels are involved in cell excitation, neuronal transmission, muscle contraction and many functions that relate directly to human diseases. Sodium channels--glycosylated proteins with a relative molecular mass of about 300,000 (ref. 5)--are responsible for signal transduction and amplification, and are chief targets of anaesthetic drugs and neurotoxins. Here we present the three-dimensional structure of the voltage-sensitive sodium channel from the eel Electrophorus electricus. The 19 A structure was determined by helium-cooled cryo-electron microscopy and single-particle image analysis of the solubilized sodium channel. The channel has a bell-shaped outer surface of 135 A in height and 100 A in side length at the square-shaped bottom, and a spherical top with a diameter of 65 A. Several inner cavities are connected to four small holes and eight orifices close to the extracellular and cytoplasmic membrane surfaces. Homologous voltage-sensitive calcium and tetrameric potassium channels, which regulate secretory processes and the membrane potential, may possess a related structure.
电压敏感膜通道、钠通道、钾通道和钙通道共同作用，在高等生物中放大、传递和产生电脉冲。钠通道和钙通道参与细胞兴奋、神经传递、肌肉收缩以及许多与人类疾病直接相关的功能。钠通道是一种糖基化蛋白，相对分子质量约为300,000（参考文献5），负责信号转导和放大，是麻醉药物和神经毒素的主要作用靶点。在此，我们展示了来自电鳗（Electrophorus electricus）的电压敏感钠通道的三维结构。通过氦冷却低温电子显微镜和对溶解的钠通道进行单颗粒图像分析，确定了其19埃的结构。该通道具有一个钟形外表面，高度为135埃，底部方形边长为100埃，顶部为球形，直径为65埃。几个内腔连接到四个小孔以及靠近细胞外和细胞质膜表面的八个孔口。调节分泌过程和膜电位的同源电压敏感钙通道和四聚体钾通道可能具有相关结构。
