Solution structure of the NEAT (NEAr Transporter) domain from IsdH/HarA: the human hemoglobin receptor in Staphylococcus aureus

J Mol Biol. 2006 Jul 7;360(2):435-47. doi: 10.1016/j.jmb.2006.05.019. Epub 2006 May 22.

Abstract

During infections the pathogen Staphylococcus aureus procures the essential nutrient iron from its host using iron-regulated surface determinant (Isd) proteins, which scavenge heme bound iron from host hemoproteins. Four Isd proteins are displayed in the cell wall, where they function as receptors for host proteins and heme. Each of the receptors contains one or more copies of a recently discovered domain called NEAT (NEAr Transporter) that has been shown to mediate protein binding. Here we report the three-dimensional solution structure of the NEAT domain from the IsdH/HarA protein, which is the hemoglobin receptor in the Isd system. This is the first structure of a NEAT domain and reveals that they adopt a beta sandwich fold that consists of two five-stranded antiparallel beta sheets. Although unrelated at the primary sequence level, our results indicate that NEAT domains belong to the immunoglobulin superfamily. Binding studies indicate that two IsdH/HarA NEAT domains bind a single molecule of methemoglobin, while the distantly related NEAT domain from the S. aureus IsdC protein binds only heme. A comparison of their primary sequences in light of the new structure is used to predict the hemoglobin and heme binding surfaces on NEAT domains.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Bacterial Proteins / chemistry*
  • Binding Sites / genetics
  • Carboxyhemoglobin / metabolism
  • Carrier Proteins / chemistry
  • Chromatography, Gel
  • Heme / metabolism
  • Humans
  • Ligands
  • Magnetic Resonance Spectroscopy
  • Methemoglobin / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Binding
  • Protein Structure, Tertiary
  • Receptors, Cell Surface / chemistry*
  • Sequence Alignment
  • Solubility
  • Staphylococcus aureus / chemistry*
  • Ultracentrifugation

Substances

  • Bacterial Proteins
  • Carrier Proteins
  • IsdC protein, Staphylococcus aureus
  • Ligands
  • Receptors, Cell Surface
  • hemoglobin-haptoglobin receptor
  • Heme
  • Methemoglobin
  • Carboxyhemoglobin

Associated data

  • PDB/2H3K