Structural and functional comparison of magnesium transporters throughout evolution.

Magnesium (Mg) is the most prevalent divalent intracellular cation. As co-factor in many enzymatic reactions, Mg is essential for protein synthesis, energy production, and DNA stability. Disturbances in intracellular Mg concentrations, therefore, unequivocally result in delayed cell growth and metabolic defects. To maintain physiological Mg levels, all organisms rely on balanced Mg influx and efflux via Mg channels and transporters. This review compares the structure and the function of prokaryotic Mg transporters and their eukaryotic counterparts. In prokaryotes, cellular Mg homeostasis is orchestrated via the CorA, MgtA/B, MgtE, and CorB/C Mg transporters. For CorA, MgtE, and CorB/C, the motifs that form the selectivity pore are conserved during evolution. These findings suggest that CNNM proteins, the vertebrate orthologues of CorB/C, also have Mg transport capacity. Whereas CorA and CorB/C proteins share the gross quaternary structure and functional properties with their respective orthologues, the MgtE channel only shares the selectivity pore with SLC41 Na/Mg transporters. In eukaryotes, TRPM6 and TRPM7 Mg channels provide an additional Mg transport mechanism, consisting of a fusion of channel with a kinase. The unique features these TRP channels allow the integration of hormonal, cellular, and transcriptional regulatory pathways that determine their Mg transport capacity. Our review demonstrates that understanding the structure and function of prokaryotic magnesiotropic proteins aids in our basic understanding of Mg transport.

© 2022. The Author(s).