Structural and functional comparison of magnesium transporters throughout evolution

Magnesium (Mg(2+)) is the most prevalent divalent intracellular cation. As co-factor in many enzymatic reactions, Mg(2+) is essential for protein synthesis, energy production, and DNA stability. Disturbances in intracellular Mg(2+) concentrations, therefore, unequivocally result in delayed cell growth and metabolic defects. To maintain physiological Mg(2+) levels, all organisms rely on balanced Mg(2+) influx and efflux via Mg(2+) channels and transporters. This review compares the structure and the function of prokaryotic Mg(2+) transporters and their eukaryotic counterparts. In prokaryotes, cellular Mg(2+) homeostasis is orchestrated via the CorA, MgtA/B, MgtE, and CorB/C Mg(2+) 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(2+) 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(2+) transporters. In eukaryotes, TRPM6 and TRPM7 Mg(2+) channels provide an additional Mg(2+) 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(2+) transport capacity. Our review demonstrates that understanding the structure and function of prokaryotic magnesiotropic proteins aids in our basic understanding of Mg(2+) transport.