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

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

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

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

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Publication Type:: Journal Article
Citation:: Journal of Biological Chemistry, 2011, 286 (44), pp. 38439 - 38447
Issue Date:: 2011-11-04

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Field	Value	Language
dc.contributor.author	Kumar, KK	en_US
dc.contributor.author	Jacques, DA https://orcid.org/0000-0002-6426-4510	en_US
dc.contributor.author	Pishchany, G	en_US
dc.contributor.author	Caradoc-Davies, T	en_US
dc.contributor.author	Spirig, T	en_US
dc.contributor.author	Malmirchegini, GR	en_US
dc.contributor.author	Langley, DB	en_US
dc.contributor.author	Dickson, CF	en_US
dc.contributor.author	Mackay, JP	en_US
dc.contributor.author	Clubb, RT	en_US
dc.contributor.author	Skaar, EP	en_US
dc.contributor.author	Guss, JM	en_US
dc.contributor.author	Gell, DA	en_US
dc.date.issued	2011-11-04	en_US
dc.identifier.citation	Journal of Biological Chemistry, 2011, 286 (44), pp. 38439 - 38447	en_US
dc.identifier.issn	0021-9258	en_US
dc.identifier.uri	http://hdl.handle.net/10453/116774
dc.description.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. © 2011 by The American Society for Biochemistry and Molecular Biology, Inc.	en_US
dc.relation.ispartof	Journal of Biological Chemistry	en_US
dc.relation.isbasedon	10.1074/jbc.M111.287300	en_US
dc.subject.classification	Biochemistry & Molecular Biology	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Staphylococcus aureus	en_US
dc.subject.mesh	Staphylococcal Infections	en_US
dc.subject.mesh	Iron	en_US
dc.subject.mesh	Bacterial Proteins	en_US
dc.subject.mesh	Hemoglobins	en_US
dc.subject.mesh	Receptors, Cell Surface	en_US
dc.subject.mesh	Antigens, Bacterial	en_US
dc.subject.mesh	Ligands	en_US
dc.subject.mesh	Crystallography, X-Ray	en_US
dc.subject.mesh	Spectrophotometry, Ultraviolet	en_US
dc.subject.mesh	Molecular Conformation	en_US
dc.subject.mesh	Protein Structure, Secondary	en_US
dc.subject.mesh	Protein Structure, Tertiary	en_US
dc.subject.mesh	Protein Binding	en_US
dc.subject.mesh	Light	en_US
dc.title	Structural basis for hemoglobin capture by Staphylococcus aureus cell-surface protein, IsdH	en_US
dc.type	Journal Article
utslib.citation.volume	44	en_US
utslib.citation.volume	286	en_US
utslib.for	1101 Medical Biochemistry and Metabolomics	en_US
utslib.for	0601 Biochemistry and Cell Biology	en_US
utslib.for	03 Chemical Sciences	en_US
utslib.for	06 Biological Sciences	en_US
utslib.for	11 Medical and Health Sciences	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
utslib.copyright.status	open_access
pubs.issue	44	en_US
pubs.publication-status	Published	en_US
pubs.volume	286	en_US

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. © 2011 by The American Society for Biochemistry and Molecular Biology, Inc.

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http://hdl.handle.net/10453/116774