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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Amino Acid Transport Systems / chemistry
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Amino Acid Transport Systems / genetics
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Bacterial Proteins / chemistry*
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Bacterial Proteins / genetics
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Binding Sites
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Cadmium / chemistry*
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Cation Transport Proteins / chemistry*
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Cation Transport Proteins / genetics
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Cations, Divalent
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Conserved Sequence
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Crystallography, X-Ray
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Escherichia coli / genetics
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Escherichia coli / metabolism
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Gene Expression
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Humans
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Ion Transport
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Iron / chemistry*
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Manganese / chemistry*
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Models, Molecular
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Molecular Sequence Data
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Protein Binding
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Protein Conformation
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Recombinant Proteins
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Staphylococcus / chemistry*
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Staphylococcus / metabolism
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Structural Homology, Protein
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Substrate Specificity
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Transcription Factors / chemistry
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Transcription Factors / genetics
Substances
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Amino Acid Transport Systems
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Bacterial Proteins
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Cation Transport Proteins
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Cations, Divalent
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DMRT1 protein
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Recombinant Proteins
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Transcription Factors
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natural resistance-associated macrophage protein 1
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Cadmium
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Manganese
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Iron