Gating the selectivity filter in ClC chloride channels
Gating the selectivity filter in ClC chloride channels
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DOI：
10.1126/science.1082708
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发表时间：
2003-04-04
期刊：
影响因子：
56.9
通讯作者：
MacKinnon, R
中科院分区：
文献类型：
--
作者：
Dutzler, R;Campbell, EB;MacKinnon, R
ClC通道通过细胞膜传导氯离子，从而控制肌肉细胞和某些神经元的电活动、跨上皮细胞的液体和电解质的运输以及细胞内小泡的酸化。研究了CLC通道选通的结构基础。野生型和突变型大肠杆菌CLC通道与单克隆Fab片段结合的晶体结构显示，在沙漏状孔的15埃长的颈部有三个氯离子结合部位。最接近胞外溶液的氯离子结合位置可以被氯离子占据，也可以被谷氨酸羧基占据。这种谷氨酸残基在鱼雷CLC通道中的突变改变了电生理检测中的门控。这些发现揭示了一种门控形式，其中谷氨酸羧基通过模仿氯离子关闭气孔。
ClC channels conduct chloride (Cl-) ions across cell membranes and thereby govern the electrical activity of muscle cells and certain neurons, the transport of fluid and electrolytes across epithelia, and the acidification of intracellular vesicles. The structural basis of ClC channel gating was studied. Crystal structures of wild-type and mutant Escherichia coli ClC channels bound to a monoclonal Fab fragment reveal three Cl- binding sites within the 15-angstrom neck of an hourglass-shaped pore. The Cl- binding site nearest the extracellular solution can be occupied either by a Cl- ion or by a glutamate carboxyl group. Mutations of this glutamate residue in Torpedo ray ClC channels alter gating in electrophysiological assays. These findings reveal a form of gating in which the glutamate carboxyl group closes the pore by mimicking a Cl- ion.