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 nearly normal growth rates on standard media (50 μM Mg2+), but the removal of all three genes created a bacterial strain requiring 100 mM external Mg2+ for normal growth. Mg2+ is transported into cells containing only the CorA transport system with similar kinetics and cation sensitivities as the Mg2+ uptake described in the earlier papers, and has additionally been quantified(see table). The uptake of Mg2+ was seen to plateau as in earlier studies, and although no actual mechanism for the decrease in transport has been determined, so it has been assumed that the protein is inactivated. Co2+ and Ni2+ are toxic to S. typhimurium cells containing a functional CorA protein and this toxicity stems from the blocking of Mg2+ uptake (competitive inhibition) and the accumulation