InterPro domain: IPR002523

This entry includes prokaryotic magnesium transport protein CorA and its related protein, zinc transport protein ZntB [ 1 ]. This entry also includes eukaryotic magnesium transporters, such as mitochondrial inner membrane magnesium transporter Mrs2 and magnesium transporter Alr1 and Alr2. These proteins are characterised by the conserved GMN motif at the end of the first of twoconserved transmembrane (TM) domains near the C terminus [ 2 ].

Thermotoga maritima CorA (TmCorA) has been reported to be an efflux system. It only has 2 TM domains,TM1 and TM2 [ 3 , 4 , 5 ]. The loop connecting TM1 and TM2 contains the conserved CorA signature motifs YGMNF and MPEL. With its N- and C-terminal ends face the cytosol and its similarity to the class II CorA (a CorA group lacking the MPEL motif and may transport divalent cations out of the cell), TmCorA is predicted to be primarily involved in ion efflux [ 5 ]. It forms a pentameric membrane protein channel featuring a possible ion discriminating aspartate ring at the cytoplasmic entrance of the pore and two distinct cytoplasmic metal binding sites per monomer, which could have regulatory roles [ 5 , 5 ].

It has been suggested that eukaryotic CorA homologues have the same topology and overall structure as T. maritima CorA [ 6 ]. In budding yeasts, Mrs2 is an essential component of the major electrophoretic Mg2+ influx system in mitochondria [ 6 ]. Overexpression of Alr1 or Alr2 increases tolerance to Al3+ and Ga3+ ions [ 7 ]. Despite generally low sequence similarity, both human Mrs2 (also known as LPE10) and S. typhimurium CorA can restore Mg2+ uptake activity in Saccharomyces cerevisiae with inactive Mrs2 [ 8 ].

1. ZntB is a novel Zn2+ transporter in Salmonella enterica serovar Typhimurium. J. Bacteriol. 184, 4369-73
2. The CorA family: structure and function revisited. Cell. Mol. Life Sci. 273, 1727-32
3. Crystal structure of a divalent metal ion transporter CorA at 2.9 angstrom resolution. Science 313, 354-7
4. Structure, properties and regulation of magnesium transport proteins. Biometals 64, 2564-74
5. Exploring the structure and function of Thermotoga maritima CorA reveals the mechanism of gating and ion selectivity in Co2+/Mg2+ transport. Biochem. J. 15, 261-70
6. Mrs2p is an essential component of the major electrophoretic Mg2+ influx system in mitochondria. EMBO J.
7. Overexpression of the Saccharomyces cerevisiae magnesium transport system confers resistance to aluminum ion. J. Biol. Chem. 22, 1235-44