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A biological role for prokaryotic ClC chloride channels

Abstract

An unexpected finding emerging from large-scale genome analyses is that prokaryotes express ion channels belonging to molecular families long studied in neurons. Bacteria and archaea are now known to carry genes for potassium channels of the voltage-gated, inward rectifier and calcium-activated classes1,2,3, ClC-type chloride channels4, an ionotropic glutamate receptor5 and a sodium channel6. For two potassium channels and a chloride channel, these homologues have provided a means to direct structure determination3,7,8,9. And yet the purposes of these ion channels in bacteria are unknown. Strong conservation of functionally important sequences from bacteria to vertebrates, and of structure itself10, suggests that prokaryotes use ion channels in roles more adaptive than providing high-quality protein to structural biologists. Here we show that Escherichia coli uses chloride channels of the widespread ClC family in the extreme acid resistance response. We propose that the channels function as an electrical shunt for an outwardly directed virtual proton pump that is linked to amino acid decarboxylation.

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Figure 1: Survival after extreme acid challenge.
Figure 2: Transport of amino acids under acid shock.
Figure 3: Model of Cl- channel involvement in XAR.
Figure 4: Activation of eriC channels at low pH.

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Acknowledgements

We are grateful to S. Lovett and V. Sutera for help with gene deletions; to C. Williams for technical assistance; and to C. Nimigean for comments on the manuscript.

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Correspondence to Christopher Miller.

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Iyer, R., Iverson, T., Accardi, A. et al. A biological role for prokaryotic ClC chloride channels. Nature 419, 715–718 (2002). https://doi.org/10.1038/nature01000

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