Ca(2+) efflux facilitated by co-transport of inorganic phosphate anion in the H(+)/Ca(2+) antiporter YfkE

Ca(2+) is an important signaling messenger. In microorganisms, fungi, and plants, H(+)/Ca(2+) antiporters (CAX) are known to play key roles in the homeostasis of intracellular Ca(2+) by catalyzing its efflux across the cell membrane. Here, we reveal that the bacterial CAX homolog YfkE transports Ca(2+) in two distinct modes: a low-flux H(+)/Ca(2+) exchange mode and a high-flux mode in which Ca(2+) and phosphate ions are co-transported (1:1) in exchange for H(+). Coupling with phosphate greatly accelerates the Ca(2+) efflux activity of YfkE. Our studies reveal that Ca(2+) and phosphate bind to adjacent sites in a central translocation pathway and lead to mechanistic insights that explain how this CAX alters its conserved alpha-repeat motifs to adopt phosphate as a specific “transport chaperon” for Ca(2+) translocation. This finding uncovers a co-transport mechanism within the CAX family that indicates this class of proteins contributes to the cellular homeostasis of both Ca(2+) and phosphate.