Structural basis for hemoglobin capture by Staphylococcus aureus cell-surface protein, IsdH.

Krishna Kumar K, Jacques DA, Pishchany G, Caradoc-Davies T, Spirig T, Malmirchegini GR, Langley DB, Dickson CF, Mackay JP, Clubb RT, Skaar EP, Guss JM, Gell DA
J Biol Chem. 2011 286 (44): 38439-47

PMID: 21917915 · PMCID: PMC3207429 · DOI:10.1074/jbc.M111.287300

Pathogens must steal iron from their hosts to establish infection. In mammals, hemoglobin (Hb) represents the largest reservoir of iron, and pathogens express Hb-binding proteins to access this source. Here, we show how one of the commonest and most significant human pathogens, Staphylococcus aureus, captures Hb as the first step of an iron-scavenging pathway. The x-ray crystal structure of Hb bound to a domain from the Isd (iron-regulated surface determinant) protein, IsdH, is the first structure of a Hb capture complex to be determined. Surface mutations in Hb that reduce binding to the Hb-receptor limit the capacity of S. aureus to utilize Hb as an iron source, suggesting that Hb sequence is a factor in host susceptibility to infection. The demonstration that pathogens make highly specific recognition complexes with Hb raises the possibility of developing inhibitors of Hb binding as antibacterial agents.

MeSH Terms (16)

Antigens, Bacterial Bacterial Proteins Crystallography, X-Ray Hemoglobins Humans Iron Ligands Light Molecular Conformation Protein Binding Protein Structure, Secondary Protein Structure, Tertiary Receptors, Cell Surface Spectrophotometry, Ultraviolet Staphylococcal Infections Staphylococcus aureus

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