ClC氯离子通道的离子转运途径和门控
Ion Transit Pathways and Gating in ClC Chloride Channels
摘要：
ClC氯离子通道具有同源二聚体结构，其中每个单体含有独立的氯离子通路。ClC通道门控受氯离子浓度、pH和电压调节。基于结构和生理学证据，已经提出选择性过滤器的细胞外末端上的谷氨酸残基充当快速门。我们利用一种新的搜索算法，结合静电信息，探索通过野生型和突变型细菌ClC通道的离子转运途径。氯离子渗透途径的检查支持谷氨酸残基在门控中的重要作用。一个外部的氯离子结合位点先前假定在生理实验中位于附近的一个保守的碱性残基相邻的门。此外，发现质子迁移到门的通路，使pH值控制在超极化膜电位。pH依赖性门控机制需要选择性过滤器中的氯离子。
英文摘要：
ClC chloride channels possess a homodimeric structure in which each monomer contains an independent chloride ion pathway. ClC channel gating is regulated by chloride ion concentration, pH, and voltage. Based on structural and physiological evidence, it has been proposed that a glutamate residue on the extracellular end of the selectivity filter acts as a fast gate. We utilize a new search algorithm which incorporates electrostatic information to explore the ion transit pathways through wild-type and mutant bacterial ClC channels. Examination of the chloride ion permeation pathways supports the proposed important role of the glutamate residue in gating. An external chloride binding site previously postulated in physiological experiments is located near a conserved basic residue adjacent to the gate. In addition, access pathways are found for proton migration to the gate, enabling pH control at hyperpolarized membrane potentials. A chloride ion in the selectivity filter is required for the pH-dependent gating mechanism.
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