The CorA gene and its corresponding protein are the most exhaustively studied Mg²⁺ transport system in any organism.
Most of the published literature on the CorA gene comes from the laboratory of M. E. Maguire.
Recently the group of R. J. Schweyen made a significant impact on the understanding of Mg²⁺ transport by CorA. The gene was originally named after the cobalt-resistant phenotype in E. coli that was caused by the gene's inactivation.

The gene was genetically identified in E. coli by Park et al.,
but wasn't cloned until Hmiel et al.
isolated the Salmonella enterica serovar Typhimurium (S. typhimurium) homologue.
Later it would be shown by Smith and Maguire that the CorA gene was present in 17 gram-negative bacteria.
With the large number of complete genome sequences now available for prokaryotes, CorA has been shown to be virtually ubiquitous among the Eubacteria, as well as being widely distributed among the Archaea.
The CorA locus in E. coli contains a single open reading frame of 948 nucleotides, producing a protein of 316 amino acids.
This protein is well conserved amongst the Eubacteria and Archaea.
Between E. coli and S. typhimurium, the proteins are 98% identical, but in more distantly related species, the similarity falls to between 15 and 20%.
In the more distantly related genes, the similarity is often restricted to the C-terminal part of the protein, and a short amino acid motif GMN within this region is very highly conserved.
The CorA domain, also known as PF01544 in the pFAM conserved protein domain database (http://webarchive.loc.gov/all/20110506030957/http%3A//pfam.sanger.ac.uk/), is additionally present in a wide range of higher organisms, and these transporters will be reviewed below.

The CorA gene is constitutively expressed in S. typhimurium under a wide range of external Mg²⁺ concentrations.
However, recent evidence suggests that the activity of the protein may be regulated by the PhoPQ two-component regulatory system.
This sensor responds to low external Mg²⁺ concentrations during the infection process of S. typhimurium in humans.
In low external Mg²⁺ conditions, the PhoPQ system was reported to suppress the function of CorA and it has been previously shown that the transcription of the alternative Mg²⁺ transporters MgtA and MgtB is activated in these conditions.
Chamnongpol and Groisman suggest that this allows the bacteria to escape metal ion toxicity caused by the transport of other ions, particularly Fe(II), by CorA in the absence of Mg²⁺. Papp and Maguire offer a conflicting report on the source of the toxicity.

The figure (not to scale) shows the originally published transmembrane (TM) domain topology of the S. typhimurium CorA protein, which was said to have three membrane-spanning regions in the C-terminal part of the protein (shown in blue), as determined by Smith et al.. Evidence for CorA acting as a homotetramer was published by Warren et al.
in 2004.
In December 2005 the crystal structure of the CorA channel was posted to the RSCB protein structure database.
The results showed that the protein has two TM domains and exists as a homopentamer, in direct conflict with the earlier reports.
Follow this link to see the structure in 3D. The soluble intracellular parts of the protein are highly charged, containing 31 positively charged and 53 negatively charged residues.
Conversely, the TM domains contain only one charged amino acid, which has been shown to be unimportant in the activity of the transporter.
From mutagenesis experiments, it appears that the chemistry of the Mg²⁺ transport relies on the hydroxyl groups lining the inside of the transport pore; there is also an absolute requirement for the GMN motif (shown in red).

Before the activity of CorA could be studied in vivo, any other Mg²⁺ transport systems in the bacterial host had to be identified and inactivated or deleted (see below).
A strain of S. typhimurium containing a functional CorA gene but lacking MgtA and MgtB was constructed(also see below), and the uptake kinetics of the transporter were analysed.
This strain showed nea
The CorA gene and its corresponding protein are the most exhaustively studied Mg²⁺ transport system in any organism. Most of the published literature on the CorA gene comes from the laboratory of M. E. Maguire. Recently the group of R. J. Schweyen made a significant impact on the understanding of Mg²⁺ transport by CorA. The gene was originally named after the cobalt-resistant phenotype in E. coli that was caused by the gene's inactivation.
The gene was genetically identified in E. coli by Park et al., but wasn't cloned until Hmiel et al. isolated the Salmonella enterica serovar Typhimurium (S. typhimurium) homologue. Later it would be shown by Smith and Maguire that the CorA gene was present in 17 gram-negative bacteria. With the large number of complete genome sequences now available for prokaryotes, CorA has been shown to be virtually ubiquitous among the Eubacteria, as well as being widely distributed among the Archaea. The CorA locus in E. coli contains a single open reading frame of 948 nucleotides, producing a protein of 316 amino acids. This protein is well conserved amongst the Eubacteria and Archaea. Between E. coli and S. typhimurium, the proteins are 98% identical, but in more distantly related species, the similarity falls to between 15 and 20%. In the more distantly related genes, the similarity is often restricted to the C-terminal part of the protein, and a short amino acid motif GMN within this region is very highly conserved. The CorA domain, also known as PF01544 in the pFAM conserved protein domain database (http://webarchive.loc.gov/all/20110506030957/http%3A//pfam.sanger.ac.uk/), is additionally present in a wide range of higher organisms, and these transporters will be reviewed below.
The CorA gene is constitutively expressed in S. typhimurium under a wide range of external Mg²⁺ concentrations. However, recent evidence suggests that the activity of the protein may be regulated by the PhoPQ two-component regulatory system. This sensor responds to low external Mg²⁺ concentrations during the infection process of S. typhimurium in humans. In low external Mg²⁺ conditions, the PhoPQ system was reported to suppress the function of CorA and it has been previously shown that the transcription of the alternative Mg²⁺ transporters MgtA and MgtB is activated in these conditions. Chamnongpol and Groisman suggest that this allows the bacteria to escape metal ion toxicity caused by the transport of other ions, particularly Fe(II), by CorA in the absence of Mg²⁺. Papp and Maguire offer a conflicting report on the source of the toxicity.
The figure (not to scale) shows the originally published transmembrane (TM) domain topology of the S. typhimurium CorA protein, which was said to have three membrane-spanning regions in the C-terminal part of the protein (shown in blue), as determined by Smith et al.. Evidence for CorA acting as a homotetramer was published by Warren et al. in 2004. In December 2005 the crystal structure of the CorA channel was posted to the RSCB protein structure database. The results showed that the protein has two TM domains and exists as a homopentamer, in direct conflict with the earlier reports. Follow this link to see the structure in 3D. The soluble intracellular parts of the protein are highly charged, containing 31 positively charged and 53 negatively charged residues. Conversely, the TM domains contain only one charged amino acid, which has been shown to be unimportant in the activity of the transporter. From mutagenesis experiments, it appears that the chemistry of the Mg²⁺ transport relies on the hydroxyl groups lining the inside of the transport pore; there is also an absolute requirement for the GMN motif (shown in red).
Before the activity of CorA could be studied in vivo, any other Mg²⁺ transport systems in the bacterial host had to be identified and inactivated or deleted (see below). A strain of S. typhimurium containing a functional CorA gene but lacking MgtA and MgtB was constructed(also see below), and the uptake kinetics of the transporter were analysed. This strain showed nea
Magnesium transporter