Anion pathways in CLCF fluoride/proton antiporters

Abstract

The CLCF F–/H+ antiporters can quickly reduce the intracellular F– concentration in the bacterial cells where these proteins are expressed. However, their operating mechanisms remain unclear. Here, we report the first computational study of the anion pathways in the prototypical CLCF antiporter from Enterococci casseliflavus. Our results suggest that the crystal structures of WT and E118Q are inward-open-outward-occluded, while that of V319G is inward-closed-outward-occluded. We further propose a mechanism to explain the unexpected reversal in the F–-over-Cl– selectivity in mutants where the H+ gating glutamate residue E118 is neutralized.