9.B.20 The Putative Mg2+ Transporter-C (MgtC) Family
The MgtC protein of Salmonella typhimurium is encoded by a gene found upstream of the mgtB gene and probably within the same operon (mgtCBR) with it. The MgtB protein is known to be a Mg2+-transporting P-type ATPase (TC #3.A.3). It was suggested on the basis of gene proximity without direct experimental evidence that MgtC is an auxiliary protein for MgtB function. However, in Mycobacterium tuberculosis, a close MgtC homologue is found in a region of the genome that does not encode a comparable MgtB homologue. Moreover, loss of MgtC, due to an mgtC knock-out mutation, prevents growth of the bacteria at low Mg2+ concentrations (10-50 µM) under low pH conditions (pH 6.2&151;6.8). Growth was restored at higher concentrations of Mg2+ (100 µM) (Alix and Blanc-Potard, 2007). The results are consistent with a Mg2+ uniport or a Mg2+:H+ antiport mechanism, but a transport function for MgtC has not yet been established. MgtC (but not MgtB) is essential for virulence. Synthesis is regulated by MgtR and an antisense RNA termed AmgR (Lee and Groisman, 2010). Roles of MgtC homologues in intramacrophage bacterial survival have been discussed (Alix and Blanc-Potard 2007).
The MgtC proteins of S. typhimurium and M. tuberculosis and the SapB protein of Bacillus subtilis exhibit 4-6 putative TMSs. Homologues are found in several bacteria including cyanobacteria, but not in archaea or eukaryotes. Most of these proteins are of a similar size, but a few are reported to be substantially smaller than the three proteins cited above. For example, SrpB of Synechococcus PCC7942, a cyanobacterial plasmid-encoded protein, which is transcriptionally induced by sulfur deprivation and controlled by the CysR protein, is 182 residues long. Some archaeal and bacterial homologues are large (400-600aas) and have 14 TMS in a 5+5+7 arrangement (see family proteins 9.B.20.3.1-3).
Günzel et al. (2006) have provided some characteristics of MgtC from Salmonella enterica. This protein is required for virulence in mice. They could not obtain evidence for a transport function, but noted that in eukaryotic cells, it activates the Na+, K+-ATPase. Moreover, Alix and Blanc-Potard (2007) summarize evidence that MgtC is required for the intramacrophage survival of several pathogens. They believe that this function may be unrelated to the ability of MgtC to promote survival at low Mg2+.