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.
(© 2022. The Author(s).)