Ion selectivity mechanism of the MgtE channel for Mg(2+) over Ca(2).

MgtE is a Mg(2+)-selective ion channel whose orthologs are widely distributed from prokaryotes to eukaryotes, including humans, and are important participants in the maintenance of cellular Mg(2+) homeostasis. The previous high-resolution structure determination of the MgtE transmembrane (TM) domain in complex with Mg(2+) ions revealed a recognition mechanism of MgtE for Mg(2+) ions. In contrast, the previous Ca(2+)-bound structure of the MgtE TM domain was determined only at moderate resolution (3.2 à resolution), which was insufficient to visualize the water molecules coordinated to Ca(2+) ions. Here, we showed that the metal-binding site of the MgtE TM domain binds to Mg(2+) ∼500-fold more strongly than to Ca(2+). We then determined the crystal structure of the MgtE TM domain in complex with Ca(2+) ions at a higher resolution (2.5 à resolution), revealing hexahydrated Ca(2+). These results provide mechanistic insights into the ion selectivity of MgtE for Mg(2+) over Ca(2+).