The magnesium ion, Mg2+, is essential for myriad biochemical processes and remains the only major biological ion whose transport mechanisms remain unknown. The CorA family of magnesium transporters is the primary Mg2+ uptake system of most prokaryotes1,2,3 and a functional homologue of the eukaryotic mitochondrial magnesium transporter4. Here we determine crystal structures of the full-length Thermotoga maritima CorA in an apparent closed state and its isolated cytoplasmic domain at 3.9 Å and 1.85 Å resolution, respectively. The transporter is a funnel-shaped homopentamer with two transmembrane helices per monomer. The channel is formed by an inner group of five helices and putatively gated by bulky hydrophobic residues. The large cytoplasmic domain forms a funnel whose wide mouth points into the cell and whose walls are formed by five long helices that are extensions of the transmembrane helices. The cytoplasmic neck of the pore is surrounded, on the outside of the funnel, by a ring of highly conserved positively charged residues. Two negatively charged helices in the cytoplasmic domain extend back towards the membrane on the outside of the funnel and abut the ring of positive charge. An apparent Mg2+ ion was bound between monomers at a conserved site in the cytoplasmic domain, suggesting a mechanism to link gating of the pore to the intracellular concentration of Mg2+.
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Reprints and permissions information is available at npg.nature.com/reprintsandpermissions. The authors declare no competing financial interests.
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The research was supported by grants from Genome Canada, the National Institutes of Health, the US Department of Energy, Office of Biological and Environmental Research, and the Structural Genomics Consortium. We thank M. McMillan and Y. Kim for assistance in collecting data, and A. Savchenko and the Indians and Red Wings screening teams for their guidance. We also thank C. Charky and D. Bouchard at Nextal Biotechnologies for their assistance throughout our membrane protein crystallization efforts.
Ribbon diagram of the CorA soluble domain. (JPG 62 kb)
Close-up view of the CorA periplasmic surface. (JPG 53 kb)
Secondary structure predictions of CorA homologues. (JPG 137 kb)
There are over 250 CorA homologs and around 200 Mrs2 homologs listed in the current NCBI and Swiss-Prot databases. (JPG 307 kb)
View of the electrostatic potential of the CorA surface. (JPG 59 kb)
This file contains legends to the Supplementary Figures. (DOC 30 kb)
This file contains Supplementary Methods, Table 1 and additional references. (DOC 60 kb)
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