title: Structural and mechanistic basis of proton-coupled metal ion transport in the SLC11/NRAMP family.
abstract: Secondary active transporters of the SLC11/NRAMP family catalyse the uptake of iron and manganese into cells. These proteins are highly conserved across all kingdoms of life and thus likely share a common transport mechanism. Here we describe the structural and functional properties of the prokaryotic SLC11 transporter EcoDMT. Its crystal structure reveals a previously unknown outward-facing state of the protein family. In proteoliposomes EcoDMT mediates proton-coupled uptake of manganese at low micromolar concentrations. Mutants of residues in the transition-metal ion-binding site severely affect transport, whereas a mutation of a conserved histidine located near this site results in metal ion transport that appears uncoupled to proton transport. Combined with previous results, our study defines the conformational changes underlying transition-metal ion transport in the SLC11 family and it provides molecular insight to its coupling to protons.
authors.affiliation: Department of Biochemistry, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
authors.forename: Ines A
authors.initials: IA
authors.lastname: Ehrnstorfer
authors.affiliation: Department of Biochemistry, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
authors.forename: Cristina
authors.initials: C
authors.lastname: Manatschal
authors.affiliation: Department of Biochemistry, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
authors.forename: Fabian M
authors.initials: FM
authors.lastname: Arnold
authors.affiliation: Department of Biochemistry, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
authors.forename: Juerg
authors.initials: J
authors.lastname: Laederach
authors.affiliation: Department of Biochemistry, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
authors.forename: Raimund
authors.initials: R
authors.lastname: Dutzler
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism*; D001665:Binding Sites; D027682:Cation Transport Proteins / Q000737:chemistry* / Q000378:metabolism*; D018360:Crystallography, X-Ray; D017136:Ion Transport; D008670:Metals / Q000737:chemistry*; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D011487:Protein Conformation; D011522:Protons
chemical_list: D001426:Bacterial Proteins; D027682:Cation Transport Proteins; D008670:Metals; D011522:Protons