Ion selectivity mechanism of the MgtE channel for Mg2+ over Ca2+
Xinyu Teng, Danqi Sheng, Jin Wang, Ye Yu, Motoyuki Hattori
Abstract
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 Å 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 Å resolution), revealing hexahydrated Ca 2+ . These results provide mechanistic insights into the ion selectivity of MgtE for Mg 2+ over Ca 2+ .