Insights from modeling three-dimensional structures of the human potassium and sodium channels
Insights from modeling three-dimensional structures of the human potassium and sodium channels
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DOI：
10.1021/pr049931q
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发表时间：
2004-07-01
影响因子：
4.4
通讯作者：
Chou, KC
中科院分区：
文献类型：
--
作者：
Chou, KC
离子通道允许离子穿过细胞膜。几乎所有细胞都有由离子通道跨越的细胞膜，没有离子通道，人类神经根本无法工作。离子通道是通过将亚基聚集成圆柱形结构而形成的，该结构允许有孔，从而形成一种用于离子运输的管道。在本研究中，人钾通道的亚基由四个相同的蛋白质链形成，而对于人钠通道的情况，相应的亚基实际上是由非常大但单一的蛋白质链折叠形成的四个异质结构域。由于这两个离子通道都是药物发现的重要目标，因此开发了它们孔区域的 3D（维度）结构。在3D模型的基础上，讨论了一些重要的分子生物学机制，这些机制可能会激发治疗与离子通道障碍相关的疾病（例如长QT综合征和慢性疼痛）的新策略。
Ion channels allow the movement of ions across cell membranes. Nearly all cells have membranes spanned by ion channels, without which human nerves simply would not work. Ion channels are formed by the aggregation of subunits into a cylindrical configuration that allows a pore, thus forming a kind of tube for ion trafficking. In the present study, the subunits of the human potassium channel are formed by four identical protein chains, whereas for the case of the human sodium channel, the corresponding subunits are actually four hetero-domains formed by the folding of a very large but single protein chain. Since both of the two ion channels are important targets for drug discovery, the 3D (dimensional) structures of their pore regions were developed. On the basis of the 3D models, some important molecular biological mechanisms were discussed that may stimulate novel strategies for therapeutic treatment of the diseases related to ion channel disorders, such as long QT syndrome and chronic pain.