Referenced in: none

Automatically associated channels: ClC4

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

Authors: Gennady V Miloshevsky, Ahmed Hassanein, Peter C Jordan

Journal, date & volume: Biophys. J., 2010 Mar 17 , 98, 999-1008

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/20303857

Abstract
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.