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

Kaavya Krishna Kumar, David A. Jacques, Gleb Pishchany, Tom Caradoc-Davies, Thomas Spirig, G. Reza Malmirchegini, David B Langley, Claire F. Dickson, Joel P Mackay, Robert T. Clubb, Eric P. Skaar, J Mitchell Guss, David Anthony Gell

Research output: Contribution to journalArticleResearchpeer-review

40 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)38439-38447
Number of pages9
JournalJournal of Biological Chemistry
Volume286
Issue number44
DOIs
Publication statusPublished - 4 Nov 2011
Externally publishedYes

Cite this

Kumar, K. K., Jacques, D. A., Pishchany, G., Caradoc-Davies, T., Spirig, T., Malmirchegini, G. R., ... Gell, D. A. (2011). Structural basis for hemoglobin capture by Staphylococcus aureus cell-surface protein, IsdH. Journal of Biological Chemistry, 286(44), 38439-38447. https://doi.org/10.1074/jbc.M111.287300
Kumar, Kaavya Krishna ; 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 Anthony. / Structural basis for hemoglobin capture by Staphylococcus aureus cell-surface protein, IsdH. In: Journal of Biological Chemistry. 2011 ; Vol. 286, No. 44. pp. 38439-38447.
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Kumar, KK, 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 2011, 'Structural basis for hemoglobin capture by Staphylococcus aureus cell-surface protein, IsdH', Journal of Biological Chemistry, vol. 286, no. 44, pp. 38439-38447. https://doi.org/10.1074/jbc.M111.287300

Structural basis for hemoglobin capture by Staphylococcus aureus cell-surface protein, IsdH. / Kumar, Kaavya Krishna; 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 Anthony.

In: Journal of Biological Chemistry, Vol. 286, No. 44, 04.11.2011, p. 38439-38447.

Research output: Contribution to journalArticleResearchpeer-review

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