title: Solution structure of the NEAT (NEAr Transporter) domain from IsdH/HarA: the human hemoglobin receptor in Staphylococcus aureus.
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.
authors.affiliation: Department of Chemistry and Biochemistry, UCLA-DOE Institute for Genomics and Proteomics, and the Molecular Biology Institute, University of California-Los Angeles, 611 Charles E. Young Drive, Los Angeles, CA 90095-1570, USA.
authors.forename: Rosemarie M
authors.initials: RM
authors.lastname: Pilpa
authors.forename: Evgeny A
authors.initials: EA
authors.lastname: Fadeev
authors.forename: Valerie A
authors.initials: VA
authors.lastname: Villareal
authors.forename: Melissa L
authors.initials: ML
authors.lastname: Wong
authors.forename: Martin
authors.initials: M
authors.lastname: Phillips
authors.forename: Robert T
authors.initials: RT
authors.lastname: Clubb
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry*; D001665:Binding Sites / Q000235:genetics; D002263:Carboxyhemoglobin / Q000378:metabolism; D002352:Carrier Proteins / Q000737:chemistry; D002850:Chromatography, Gel; D006418:Heme / Q000378:metabolism; D006801:Humans; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008706:Methemoglobin / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011956:Receptors, Cell Surface / Q000737:chemistry*; D016415:Sequence Alignment; D012995:Solubility; D013211:Staphylococcus aureus / Q000737:chemistry*; D014461:Ultracentrifugation
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; C488727:IsdC protein, Staphylococcus aureus; D008024:Ligands; D011956:Receptors, Cell Surface; C027079:hemoglobin-haptoglobin receptor; D006418:Heme; D008706:Methemoglobin; D002263:Carboxyhemoglobin