Antiport mechanism for Cl(-)/H(+) in ClC-ec1 from normal-mode analysis.

Biophys J

School of Nuclear Engineering, Purdue University, West Lafayette, Indiana, USA.

Published: March 2010

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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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2849085PMC
http://dx.doi.org/10.1016/j.bpj.2009.11.035DOI Listing

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