Iron is the most abundant trace element in the human body. Its uptake into cells is mediated by secondary-active transporters of the SLC11/NRAMP family. These transporters are expressed in all kingdoms of life where they mediate the H+-coupled cotransport of iron or other transition metals such as Mn2+. We have previously determined the structures of close prokaryotic homologues of the family by X-ray crystallography and characterized their transport properties by biochemical assays24,25. These studies have defined the structure of the transporter in inward- and outward-facing conformations, revealed the structure of a transition metal binding site and provided initial insight into the coupling to H+. In ongoing work, we have extended our focus towards other family members to investigate the detailed mechanisms of ion selectivity. These studies include studies on inhibition of the human SLC11 transporter DMT1 as a potential strategy against iron overload disorders. Our research on this protein family is supported by the NCCR TransCure.
24 Ehrnstorfer, I. A., Geertsma, E. R., Pardon, E., Steyaert, J. & Dutzler, R. Crystal structure of a SLC11 (NRAMP) transporter reveals the basis for transition-metal ion transport. Nat. Struct. Mol. Biol. 21 (2014).
25 Ehrnstorfer, I. A., Manatschal, C., Arnold, F. M., Laederach, J. & Dutzler, R. Structural and mechanistic basis of proton-coupled metal ion transport in the SLC11/NRAMP family. Nat. Commun. 8, 14033, doi:10.1038/ncomms14033 (2017).