Structural basis for hemoglobin capture by Staphylococcus aureus cell-surface protein, IsdH |
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Authors: | Krishna Kumar Kaavya Jacques David A Pishchany Gleb Caradoc-Davies Tom Spirig Thomas Malmirchegini G Reza Langley David B Dickson Claire F Mackay Joel P Clubb Robert T Skaar Eric P Guss J Mitchell Gell David A |
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Institution: | School of Molecular Bioscience, University of Sydney, New South Wales 2006, Australia. |
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Abstract: | 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. |
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