Q-cubed mutant cues clues to CLC antiport mechanism.
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ABSTRACT:
SUBMITTER: Miller C
PROVIDER: S-EPMC7894039 | biostudies-literature | 2021 Apr
REPOSITORIES: biostudies-literature
Publications
Q-cubed mutant cues clues to CLC antiport mechanism.
The Journal of general physiology 20210401 4
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Project description:ClC chloride channels and transporters play major roles in cellular excitability, epithelial salt transport, volume, pH, and blood pressure regulation. One family member, ClC-ec1 from Escherichia coli, has been structurally resolved crystallographically and subjected to intensive mutagenetic, crystallographic, and electrophysiological studies. It functions as a Cl(-)/H(+) antiporter, not a Cl(-) channel; however, the molecular mechanism for Cl(-)/H(+) exchange is largely unknown. Using all-atom normal-mode analysis to explore possible mechanisms for this antiport, we propose that Cl(-)/H(+) exchange involves a conformational cycle of alternating exposure of Cl(-) and H(+) binding sites of both ClC pores to the two sides of the membrane. Both pores switch simultaneously from facing outward to facing inward, reminiscent of the standard alternating-access mechanism, which may have direct implications for eukaryotic Cl(-)/H(+) transporters and Cl(-) channels.
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