Structural and functional comparison of magnesium transporters throughout evolution

Magnesium (Mg2+) is the most prevalent divalent intracellular cation. As co-factor in many enzymatic reactions, Mg2+ is essential for protein synthesis, energy production, and DNA stability. Disturbances in intracellular Mg2+ concentrations, therefore, unequivocally result in delayed cell growth and metabolic defects. To maintain physiological Mg2+ levels, all organisms rely on balanced Mg2+ influx and efflux via Mg2+ channels and transporters. This review compares the structure and the function of prokaryotic Mg2+ transporters and their eukaryotic counterparts. In prokaryotes, cellular Mg2+ homeostasis is orchestrated via the CorA, MgtA/B, MgtE, and CorB/C Mg2+ 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 Mg2+ 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+/Mg2+ transporters. In eukaryotes, TRPM6 and TRPM7 Mg2+ channels provide an additional Mg2+ 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 Mg2+ transport capacity. Our review demonstrates that understanding the structure and function of prokaryotic magnesiotropic proteins aids in our basic understanding of Mg2+ transport.

Automated summary

Magnesium plays a vital role in cellular processes and disturbances in its levels can result in cell growth delay and metabolic defects. This review compares the structure and function of magnesium transporters in prokaryotes and eukaryotes, highlighting the conserved motifs and selectivity pore. It also discusses the unique features of TRP channels in eukaryotes that contribute to magnesium transport capacity.