Ion selectivity mechanism of the MgtE channel for Mg2+ over Ca2

Xinyu Teng; Danqi Sheng; Jin Wang; Ye Yu; Motoyuki Hattori

doi:10.1016/j.isci.2022.105565

Ion selectivity mechanism of the MgtE channel for Mg²⁺ over Ca²

iScience. 2022 Nov 13;25(12):105565. doi: 10.1016/j.isci.2022.105565. eCollection 2022 Dec 22.

Authors

Xinyu Teng¹, Danqi Sheng¹, Jin Wang², Ye Yu², Motoyuki Hattori¹

Affiliations

¹ 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.
² School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Medical Building, Room 128, 639 Long-Mian Road, Nanjing 200098, China.

Abstract

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⁺.

Keywords: Biochemistry; Ion; Protein.