MgtA and MgtB: prokaryotic P-type ATPases that mediate Mg2+ influx.
The gram-negative bacterium Salmonella typhimurium possesses three distinct Mg2+ transport systems, encoded by the corA, mgtA, and mgtB loci. The CorA transport system is the constitutive Mg2+ influx system. It can also mediate Mg2+ efflux at very high extracellular Mg2+ concentrations. In contrast, the MgtA and MgtB Mg2+ transport systems are normally expressed only at low extracellular Mg2+ concentrations. A strain of S. typhimurium was constructed by mutagenesis which lacks Mg2+ transport and requires 100 mM Mg2+ for growth. Using this strain, both the MgtA and MgtB transport systems were cloned by complementation of the strains inability to grow without Mg2+ supplementation. After sequencing and further genetic analysis, the MgtB system appears to be an operon composed of the mgtC and mgtB genes (5' to 3'). The downstream mgtB gene encodes the 102 kDa MgtB protein which by sequence analysis is clearly a P-type ATPase. Interestingly, while MgtB has relatively poor homology to other known prokaryotic P-type ATPases, it is highly homologous to mammalian reticular Ca(2+)-ATPases. MgtC is a 22.5 kDa hydrophobic membrane protein that lacks homology to any known protein. Transposon insertions in this gene abolish uptake by the MgtB transport system. We hypothesize that MgtC is a subunit of the MgtB ATPase involved either in proper insertion of MgtB into the membrane or possibly in binding of extracellular Mg2+ for delivery to the ATPase subunit. The sequence of the MgtA gene has recently been completed, and it too is a P-type ATPase more similar to eukaryotic than prokaryotic P-type ATPases. Expression of both MgtA and MgtB are highly regulated by the concentration of extracellular Mg2+. Transcription of mgtB can be increased about 1000 fold by lowering Mg2+ from 1 mM to 1 microM. Likewise, when mgtB is expressed from a multicopy plasmid, a similar decrease in extracellular Mg2+ greatly increases transport. Under growth conditions of limiting Mg2+, MgtB becomes the dominant Mg2+ influx system in S. typhimurium. Even so, since MgtB (and MgtA) mediate only influx of Mg2+, it is unclear why the cell requires energy from ATP to mediate Mg2+ entry into the cell down a large electrochemical gradient. Further studies of the structure-function and energetics of these novel Mg2+ influx P-type ATPases should yield insights into the function of P-type ATPases in general as well as information about the regulation of cellular Mg2+ fluxes.
Maguire
M E
ME
Department of Pharmacology, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106-4965.
D000251:Adenosine Triphosphatases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D005075:Biological Evolution; D015964:Gene Expression Regulation, Bacterial; D016623:Ion Pumps; D008274:Magnesium / Q000378:metabolism*; D011487:Protein Conformation; D012486:Salmonella typhimurium / Q000201:enzymology* / Q000235:genetics
D016623:Ion Pumps; D000251:Adenosine Triphosphatases; D008274:Magnesium