Insights from modeling three-dimensional structures of the human potassium and sodium channels

被引:98
作者
Chou, KC [1 ]
机构
[1] Shanghai Jiao Tong Univ, Life Sci Res Ctr, Shanghai 200030, Peoples R China
[2] TIBDD, Tianjin 300074, Peoples R China
[3] Gordon Life Sci Inst, San Diego, CA USA
关键词
pore region; membrane-spanning protein; channel architecture; pore; selectivity filter; HERG; hPN3;
D O I
10.1021/pr049931q
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:856 / 861
页数:6
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