Ion selectivity mechanism of the MgtE channel for Mg2+ over Ca2+
Xinyu Teng,
Danqi Sheng,
Jin Wang,
Ye Yu,
Motoyuki Hattori
Affiliations
Xinyu Teng
State Key Laboratory of Genetic Engineering, Collaborative Innovation Center of Genetics and Development, Shanghai Key Laboratory of Bioactive Small Molecules, Department of Physiology and Neurobiology, School of Life Sciences, Fudan University, Shanghai 200438, China
Danqi Sheng
State Key Laboratory of Genetic Engineering, Collaborative Innovation Center of Genetics and Development, Shanghai Key Laboratory of Bioactive Small Molecules, Department of Physiology and Neurobiology, School of Life Sciences, Fudan University, Shanghai 200438, China
Jin Wang
School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Medical Building, Room 128, 639 Long-Mian Road, Nanjing 200098, China
Ye Yu
School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Medical Building, Room 128, 639 Long-Mian Road, Nanjing 200098, China
Motoyuki Hattori
State Key Laboratory of Genetic Engineering, Collaborative Innovation Center of Genetics and Development, Shanghai Key Laboratory of Bioactive Small Molecules, Department of Physiology and Neurobiology, School of Life Sciences, Fudan University, Shanghai 200438, China; Corresponding author
Summary: MgtE is a Mg2+-selective ion channel whose orthologs are widely distributed from prokaryotes to eukaryotes, including humans, and are important participants in the maintenance of cellular Mg2+ homeostasis. The previous high-resolution structure determination of the MgtE transmembrane (TM) domain in complex with Mg2+ ions revealed a recognition mechanism of MgtE for Mg2+ ions. In contrast, the previous Ca2+-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 Ca2+ ions. Here, we showed that the metal-binding site of the MgtE TM domain binds to Mg2+ ∼500-fold more strongly than to Ca2+. We then determined the crystal structure of the MgtE TM domain in complex with Ca2+ ions at a higher resolution (2.5 Å resolution), revealing hexahydrated Ca2+. These results provide mechanistic insights into the ion selectivity of MgtE for Mg2+ over Ca2+.
