Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.
Magnesium Transporters: Properties, Regulation and Structure
The chemistry of Mg2+ is unique amongst biological cations, and the properties of Mg2+ transport systems reflect this chemistry. Prokaryotes carry three classes of Mg2+ transport systems: CorA, MgtA/B and MgtE. CorA and MgtE are widely distributed in both Eubacteria and Archaea, while the MgtA/B class is found primarily in the Eubacteria. Eukaryotic homologs of CorA, although clearly functional as Mg2+ transporters, have minimal sequence homology and include the Mrs2p mitochondrial Mg2+ channel and the ALR proteins of fungi. MgtE homologs are more recognizable in eukaryotes as the SLC41 class of transporters. The MgtA/B Mg2+ transporters belong to the P-type ATPase superfamily, but mediate Mg2+ influx down its electrochemical gradient rather than against the gradient as with other P-type ATPases. Their physiological role is not clear. CorA is the only Mg2+ transporter whose structure has been solved. It is a homopentamer with two transmembrane domains per monomer, the first of which forms the ion conduction pathway. Mg2+ transport involves first the binding of the fully hydrated cation to an extracellular binding loop connecting the transmembrane domains. Passage through the membrane involves no electrostatic interactions, but two cytosolic domains, one carrying extremely high concentrations of positive charge and the other negative charge appear to help control Mg2+ flux, in concert with an intracellular Mg2+ bound between domains of each monomer. Neither CorA nor MgtE appear to be transcriptionally regulated, implying they are primarily "housekeeping" genes. Nonetheless, mutation of the corA gene in Salmonella enterica serovar Typhimurium leads to attenuation of virulence and other defects, even though the strain carries two additional Mg2+ transporters and the mutant exhibits no Mg2+-dependent growth deficit.