Fig. 6.

Proposed mechanism of Ca²⁺/H⁺ exchange by YfkE. (A) Inward open conformation stabilized by the protonated residue E255 for Ca²⁺ access. Conformational changes of the residues E255 and H256 may generate a path for Ca²⁺ binding and also shift TM2a for closure of the cytoplasmic entry. (B) Ca²⁺ binding at the oxygen umbrella leads to a rearrangement of the binding site, inducing conformational changes in TMs 7a and 6 (not shown for clarity) to transit the protein into an outward-facing conformation. (C) The residue E72 transfers H⁺ (blue sphere) from the periplasmic surface to the Ca²⁺-binding site. Ca²⁺ release is then triggered by protonation of E255 and/or H256, which may also reset the protein back to the inward-facing conformation.