X-ray structure of a CIC chloride channel at 3.0 Å reveals the molecular basis of anion selectivity
X-ray structure of a CIC chloride channel at 3.0 Å reveals the molecular basis of anion selectivity
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DOI：
10.1038/415287a
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发表时间：
2002-01-17
期刊：
影响因子：
64.8
通讯作者：
MacKinnon, R
中科院分区：
文献类型：
--
作者：
Dutzler, R;Campbell, EB;MacKinnon, R
ClC 氯化物通道催化 Cl- 离子选择性地穿过细胞膜，从而调节骨骼肌的电激发以及盐和水穿过上皮屏障的流动。 ClC Cl-通道的遗传缺陷是多种家族性肌肉和肾脏疾病的基础。在这里，我们展示了来自鼠伤寒沙门氏菌和大肠杆菌的两个原核 ClC Cl- 通道，分别在 3.0 和 3.5 埃处的 X 射线结构。两种结构都显示出两个相同的孔，每个孔均由同型二聚体膜蛋白内包含的单独亚基形成。各个亚基由两个大致重复的半部分组成，它们以相反的方向横跨膜。这种反平行结构定义了一种选择性过滤器，其中Cl-离子通过与α-螺旋偶极子的静电相互作用以及通过与氮原子和羟基的化学配位来稳定。这些发现为进一步了解ClC Cl-通道的功能提供了结构基础，并建立了其阴离子选择性的物理和化学基础。
The ClC chloride channels catalyse the selective flow of Cl- ions across cell membranes, thereby regulating electrical excitation in skeletal muscle and the flow of salt and water across epithelial barriers. Genetic defects in ClC Cl- channels underlie several familial muscle and kidney diseases. Here we present the X-ray structures of two prokaryotic ClC Cl- channels from Salmonella enterica serovar typhimurium and Escherichia coli at 3.0 and 3.5 Angstrom, respectively. Both structures reveal two identical pores, each pore being formed by a separate subunit contained within a homodimeric membrane protein. Individual subunits are composed of two roughly repeated halves that span the membrane with opposite orientations. This antiparallel architecture defines a selectivity filter in which a Cl- ion is stabilized by electrostatic interactions with a-helix dipoles and by chemical coordination with nitrogen atoms and hydroxyl groups. These findings provide a structural basis for further understanding the function of ClC Cl- channels, and establish the physical and chemical basis of their anion selectivity.