The Unique Nature of Mg2+ Channels

Andrea S. Moomaw and Michael E. Maguire Department of Pharmacology, School of Medicine, Case Western Reserve University, Cleveland, Ohio andrea.moomaw{at}case.edu Considering the biological abundance and importance of Mg 2+ , there is a surprising lack of information regarding the proteins that transport Mg 2+ , the mechanisms by which they do so, and their physiological roles within the cell. The best characterized Mg 2+ channel to date is the bacterial protein CorA, present in a wide range of bacterial species. The CorA homolog Mrs2 forms the mitochondrial Mg 2+ channel in all eukaryotes. Physiologically, CorA is involved in bacterial pathogenesis, and the Mrs2 eukaryotic homolog is essential for cell survival. A second Mg 2+ channel widespread in bacteria is MgtE. Its eukaryotic homologs are the SLC41 family of carriers. Physiological roles for MgtE and its homologs have not been established. Recently, the crystal structures for the bacterial CorA and MgtE Mg 2+ channels were solved, the first structures of any divalent cation channel. As befits the unique biological chemistry of Mg 2+ , both structures are unique, unlike that of any other channel or transporter. Although structurally quite different, both CorA and MgtE appear to be gated in a similar manner through multiple Mg 2+ binding sites in the cytosolic domain of the channels. These sites essentially serve as Mg 2+ "sensors" of cytosolic Mg 2+ concentration. Many questions about these channels remain, however, including the molecular basis of Mg 2+ selectivity and the physiological role(s) of their eukaryotic homologs.