Crystal structure of a SLC11 (NRAMP) transporter reveals the basis for transition-metal ion transport

Nat Struct Mol Biol. 2014 Nov;21(11):990-6. doi: 10.1038/nsmb.2904. Epub 2014 Oct 19.


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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Amino Acid Transport Systems / chemistry
  • Amino Acid Transport Systems / genetics
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / genetics
  • Binding Sites
  • Cadmium / chemistry*
  • Cation Transport Proteins / chemistry*
  • Cation Transport Proteins / genetics
  • Cations, Divalent
  • Conserved Sequence
  • Crystallography, X-Ray
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Gene Expression
  • Humans
  • Ion Transport
  • Iron / chemistry*
  • Manganese / chemistry*
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Binding
  • Protein Conformation
  • Recombinant Proteins
  • Staphylococcus / chemistry*
  • Staphylococcus / metabolism
  • Structural Homology, Protein
  • Substrate Specificity
  • Transcription Factors / chemistry
  • Transcription Factors / genetics


  • Amino Acid Transport Systems
  • Bacterial Proteins
  • Cation Transport Proteins
  • Cations, Divalent
  • DMRT1 protein
  • Recombinant Proteins
  • Transcription Factors
  • natural resistance-associated macrophage protein 1
  • Cadmium
  • Manganese
  • Iron

Associated data

  • PDB/4WGV
  • PDB/4WGW