Abstract
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.
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Acknowledgements
We are grateful to C. Williams, B Bablouzion and L. Kolmakova-Partensky for technical assistance, to C. Nimigean for advice throughout the course of this work, and to M. Walden for help with fluorescence measurements. We also thank P. De Weer, F. M. Ashcroft and G. Yellen for critical readings of the manuscript.
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Accardi, A., Miller, C. Secondary active transport mediated by a prokaryotic homologue of ClC Cl- channels. Nature 427, 803–807 (2004). https://doi.org/10.1038/nature02314
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DOI: https://doi.org/10.1038/nature02314
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