Secondary active transport mediated by a prokaryotic homologue of ClC Cl- channels
Secondary active transport mediated by a prokaryotic homologue of ClC Cl- channels
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DOI：
10.1038/nature02314
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发表时间：
2004-02-26
期刊：
影响因子：
64.8
通讯作者：
Miller, C
中科院分区：
文献类型：
--
作者：
Accardi, A;Miller, C
ClC - Cl-通道构成了一个大分子家族，在生物体和细胞类型中普遍存在。在真核生物中，这些通道完成了许多需要门控阴离子传导的生物学作用，从调节骨骼肌兴奋性到促进（H+） atp酶的内体酸化。在原核生物中，除大肠杆菌外，ClC的功能尚不清楚，在大肠杆菌中，ClC- ec1蛋白促进H+挤压，激活了肠道细菌常见的极端耐酸反应。近年来，利用x射线晶体学研究了ClC- ec1的高分辨率结构。这种原始的原核小细胞肺癌结构有效地指导了对广泛研究的真核小细胞肺癌通道中的门控和阴离子渗透的理解。我们现在表明这种细菌同源物不是离子通道，而是一个H+- cl交换转运体。由于相同的分子结构可以支持两种根本不同的转运机制，因此分离通道和转运体的结构边界似乎并不像通常认为的那样明确。
ClC Cl- channels make up a large molecular family, ubiquitous with respect to both organisms and cell types. In eukaryotes, these channels fulfill numerous biological roles requiring gated anion conductance, from regulating skeletal muscle excitability to facilitating endosomal acidification by (H+) ATPases. In prokaryotes, ClC functions are unknown except in Escherichia coli, where the ClC- ec1 protein promotes H+ extrusion activated in the extreme acid-resistance response common to enteric bacteria. Recently, the high-resolution structure of ClC- ec1 was solved by X-ray crystallography. This primal prokaryotic ClC structure has productively guided understanding of gating and anion permeation in the extensively studied eukaryotic ClC channels. We now show that this bacterial homologue is not an ion channel, but rather a H+-Cl- exchange transporter. As the same molecular architecture can support two fundamentally different transport mechanisms, it seems that the structural boundary separating channels and transporters is not as clear cut as generally thought.