title: Crystal structure of a SLC11 (NRAMP) transporter reveals the basis for transition-metal ion transport.
abstract: Members of the SLC11 (NRAMP) family transport iron and other transition-metal ions across cellular membranes. These membrane proteins are present in all kingdoms of life with a high degree of sequence conservation. To gain insight into the determinants of ion selectivity, we have determined the crystal structure of Staphylococcus capitis DMT (ScaDMT), a close prokaryotic homolog of the family. ScaDMT shows a familiar architecture that was previously identified in the amino acid permease LeuT. The protein adopts an inward-facing conformation with a substrate-binding site located in the center of the transporter. This site is composed of conserved residues, which coordinate Mn2+, Fe2+ and Cd2+ but not Ca2+. Mutations of interacting residues affect ion binding and transport in both ScaDMT and human DMT1. Our study thus reveals a conserved mechanism for transition-metal ion selectivity within the SLC11 family.
authors.affiliation: Department of Biochemistry, University of Zurich, Zurich, Switzerland.
authors.forename: Ines A
authors.initials: IA
authors.lastname: Ehrnstorfer
authors.affiliation: Department of Biochemistry, University of Zurich, Zurich, Switzerland.
authors.forename: Eric R
authors.initials: ER
authors.lastname: Geertsma
authors.affiliation: 1] Structural Biology Research Center, Vlaams Instituut voor Biotechnologie (VIB), Brussels, Belgium. [2] Structural Biology Brussels, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Els
authors.initials: E
authors.lastname: Pardon
authors.affiliation: 1] Structural Biology Research Center, Vlaams Instituut voor Biotechnologie (VIB), Brussels, Belgium. [2] Structural Biology Brussels, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Steyaert
authors.affiliation: Department of Biochemistry, University of Zurich, Zurich, Switzerland.
authors.forename: Raimund
authors.initials: R
authors.lastname: Dutzler
mesh_terms: D000595:Amino Acid Sequence; D026905:Amino Acid Transport Systems / Q000737:chemistry / Q000235:genetics; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics; D001665:Binding Sites; D002104:Cadmium / Q000737:chemistry*; D027682:Cation Transport Proteins / Q000737:chemistry* / Q000235:genetics; D002413:Cations, Divalent; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D017136:Ion Transport; D007501:Iron / Q000737:chemistry*; D008345:Manganese / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D011994:Recombinant Proteins; D013210:Staphylococcus / Q000737:chemistry* / Q000378:metabolism; D040681:Structural Homology, Protein; D013379:Substrate Specificity; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics; D000099173:Natural Resistance-associated Macrophage Protein 1
chemical_list: D026905:Amino Acid Transport Systems; D001426:Bacterial Proteins; D002104:Cadmium; D027682:Cation Transport Proteins; D002413:Cations, Divalent; D007501:Iron; D008345:Manganese; D011994:Recombinant Proteins; D014157:Transcription Factors; D000099173:Natural Resistance-associated Macrophage Protein 1; C110547:DMRT1 protein