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 - 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 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) summarized 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+.
MgtC is required for intramacrophage replication of intracellular pathogens and growth in low Mg2+ medium. A link between these two phenotypes has been proposed due to putative Mg2+ deprivation inside the phagosome. MgtC is part of a family of proteins that share a conserved N-terminal transmembrane domain and a variable C-terminal domain. The Salmonella MgtC C-terminal domain is cytoplasmic, adopts a fold also found in metal transporters and RNA interacting domain, and does not bind Mg2+. MgtC homologues from diverse gamma-proteobacteria have been expressed in a Salmonella ΔmgtC strain. The Y. pestis MgtC fully replaced the Salmonella MgtC whereas P. luminescens or P. aeruginosa MgtC complemented only in low Mg2+ medium, thus dissociating the two MgtC-related phenotypes.
MgtC is a dimer, bearing an ACT-like domain (Yang et al. 2012). A mutant lacking the mgtC gene exhibited increased cellulose levels due to increased expression of the cellulose synthase gene bcsA and of cyclic diguanylate, the allosteric activator of the BcsA protein (Pontes et al. 2015).
Putative Mg2+ transporter, MgtC (Retamal et al. 2009). The MgtC virulence protein binds to the F-type ATP synthase and maintains ATP homeostasis required for pathogenesis during phagosome acidification (Lee and Lee 2015). The mgtC gene, which is present in S. enterica but not in E. coli, is responsible for the differences in RpoS accumulation between these two bacterial species. Thus, bacteria possess a mechanism to control RpoS accumulation responding to cytoplasmic Mg2+ levels, the difference of which causes distinct RpoS accumulation patterns in closely related bacterial species (Park et al. 2018).
MgtC of Salmonella typhimurium
Putative Mg2+ transporter, virulence factor, MgtC. The C-terminal domain is a divergent ACT domain (Yang et al. 2012). The claim that MgtC is a Mg2+ transporter has been refuted (Yang et al. 2012).
MgtC of Mycobacterium tuberculosis
Fungal MgtC homologue (Gastebois et al. 2011).
MgtC homologue of Aspergillus fumigatus
Magnesium uptake system of 215 aas and 4 or 5 TMSs, YhiD (YhhE; MgtC). This protein seems to be a low affinity magnesium uptake protein that could function either as a channel or a carrier (Ishijima et al. 2015). It plays a role in acid resistance at high cell densities together with the 6 TMS HdeD protein that may be an organic acid exporter (TC# 9.B.36.1.1) (Mates et al. 2007). The mgtC gene, which is present in S. enterica but not in E. coli, is responsible for the differences in RpoS accumulation between these two bacterial species. Thus, bacteria possess a mechanism to control RpoS accumulation responding to cytoplasmic Mg2+ levels, the difference of which causes distinct RpoS accumulation in closely related bacterial species (Park et al. 2018).
YhiD of E. coli
MgtC of 230 aas and 4 N-terminal TMSs. Under Mg2+ limitation, P. aeruginosa MgtC prevents biofilm formation. It is expressed at high levels in macrophage and is important for multiplication inside macrophages. MgtC is required for optimal growth in Mg2+ deprived media (Bernut et al. 2015).
MgtC of Pseudomonas aeruginosa
Eukaryotic MgtC homologue, SrpB (163aas; 5 TMSs)
SrpB of Ricinus communis (B9TCJ7)
COG3174 family member (548 aas; 14 TMSs in a 5+5+4 arrangement)
COG3174 family member of Halobacterium salinarium (Q9HPQ3)
MgtC/SapB transporter (415aas; 14 TMSs in a 5+5+4 arrangement).
MgtC/SapB homologue of Halorubrum lacusprofundi (B9LV18)
Azo1681 (422aas; 14TMSs in a 5+5+4 arrangement)
Azo1681 of Azoarcus sp. BH72 (A1K643)
Uncharacterized protein of 277 aas and 9 TMSs.
UP of Bdellovibrio bacteriovorus
DUF4956 domain containing protein of 230 aas and 5 N-terminal TMSs. Within the Pfam MgtC family.
MgtC family protein of Alloprevotella rava
DUF4956 domain containing protein of 215 aas and 4 or 5 TMSs.
DUF4956 domain protein of Streptomyces kanamyceticus
Uncharacterized protein of 193 aas and 5 N-terminal TMSs.
UP of Chryseobacterium hungaricum
DUF4956 domain-containing protein of 229 aas and 3 - 4 TMSs.
DUC4956 protein of Streptococcus mutans
DUF4956 domain-containing protein of 243 aas and 3 - 4 TMSs.
DUF4956 domain protein of Endozoicomonas elysicola
Uncharacterized protein of 224 aas and 3 or 4 TMSs.
UP of Candidatus Magasanikbacteria bacterium GW2011