The Streptococcal Binding Site in the Gelatin-binding Domain of Fibronectin is Consistent with a Non-linear Arrangement of Modules

Kate E. Atkin, Andrew S. Brentnall, Gemma Harris, Richard J. Bingham, Michele C. Erat, Christopher J. Millard, Ulrich Schwarz-Linek, David Staunton, Ioannis Vakonakis, Iain D. Campbell, Jennifer R. Potts

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Fibronectin-binding proteins (FnBPs) of Staphylococcus aureus and Streptococcus pyogenes mediate invasion of human endothelial and epithelial cells in a process likely to aid the persistence and/or dissemination of infection. In addition to binding sites for the N-terminal domain (NTD) of fibronectin (Fn), a number of streptococcal FnBPs also contain an upstream region (UR) that is closely associated with an NTD-binding region; UR binds to the adjacent gelatin-binding domain (GBD) of Fn. Previously, UR was shown to be required for efficient streptococcal invasion of epithelial cells. Here we show, using a Streptococcus zooepidemicus FnBP, that the UR-binding site in GBD resides largely in the 8F19F1 module pair. We also show that UR inhibits binding of a peptide from the α1 chain of type I collagen to 8F19F1 and that UR binding to 8F1 is likely to occur through anti-parallel β-zipper formation. Thus, we propose that streptococcal proteins that contain adjacent NTD- and GBD-binding sites form a highly unusual extended tandem β-zipper that spans the two domains and mediates high affinity binding to Fn through a large intermolecular interface. The proximity of the UR- and NTD-binding sequences in streptococcal FnBPs is consistent with a non-linear arrangement of modules in the tertiary structure of the GBD of Fn.

LanguageEnglish
Pages36977-36983
Number of pages7
JournalJournal of Biological Chemistry
Volume285
Issue number47
DOIs
Publication statusPublished - 19 Nov 2010
Externally publishedYes

Fingerprint

Gelatin
Fibronectins
Binding Sites
Carrier Proteins
Fasteners
Streptococcus equi
Epithelial Cells
Streptococcus pyogenes
Endothelial cells
Collagen Type I
Staphylococcus aureus
Endothelial Cells
Peptides
Infection

Cite this

Atkin, Kate E. ; Brentnall, Andrew S. ; Harris, Gemma ; Bingham, Richard J. ; Erat, Michele C. ; Millard, Christopher J. ; Schwarz-Linek, Ulrich ; Staunton, David ; Vakonakis, Ioannis ; Campbell, Iain D. ; Potts, Jennifer R. / The Streptococcal Binding Site in the Gelatin-binding Domain of Fibronectin is Consistent with a Non-linear Arrangement of Modules. In: Journal of Biological Chemistry. 2010 ; Vol. 285, No. 47. pp. 36977-36983.
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abstract = "Fibronectin-binding proteins (FnBPs) of Staphylococcus aureus and Streptococcus pyogenes mediate invasion of human endothelial and epithelial cells in a process likely to aid the persistence and/or dissemination of infection. In addition to binding sites for the N-terminal domain (NTD) of fibronectin (Fn), a number of streptococcal FnBPs also contain an upstream region (UR) that is closely associated with an NTD-binding region; UR binds to the adjacent gelatin-binding domain (GBD) of Fn. Previously, UR was shown to be required for efficient streptococcal invasion of epithelial cells. Here we show, using a Streptococcus zooepidemicus FnBP, that the UR-binding site in GBD resides largely in the 8F19F1 module pair. We also show that UR inhibits binding of a peptide from the α1 chain of type I collagen to 8F19F1 and that UR binding to 8F1 is likely to occur through anti-parallel β-zipper formation. Thus, we propose that streptococcal proteins that contain adjacent NTD- and GBD-binding sites form a highly unusual extended tandem β-zipper that spans the two domains and mediates high affinity binding to Fn through a large intermolecular interface. The proximity of the UR- and NTD-binding sequences in streptococcal FnBPs is consistent with a non-linear arrangement of modules in the tertiary structure of the GBD of Fn.",
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Atkin, KE, Brentnall, AS, Harris, G, Bingham, RJ, Erat, MC, Millard, CJ, Schwarz-Linek, U, Staunton, D, Vakonakis, I, Campbell, ID & Potts, JR 2010, 'The Streptococcal Binding Site in the Gelatin-binding Domain of Fibronectin is Consistent with a Non-linear Arrangement of Modules', Journal of Biological Chemistry, vol. 285, no. 47, pp. 36977-36983. https://doi.org/10.1074/jbc.M110.156935

The Streptococcal Binding Site in the Gelatin-binding Domain of Fibronectin is Consistent with a Non-linear Arrangement of Modules. / Atkin, Kate E.; Brentnall, Andrew S.; Harris, Gemma; Bingham, Richard J.; Erat, Michele C.; Millard, Christopher J.; Schwarz-Linek, Ulrich; Staunton, David; Vakonakis, Ioannis; Campbell, Iain D.; Potts, Jennifer R.

In: Journal of Biological Chemistry, Vol. 285, No. 47, 19.11.2010, p. 36977-36983.

Research output: Contribution to journalArticle

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T1 - The Streptococcal Binding Site in the Gelatin-binding Domain of Fibronectin is Consistent with a Non-linear Arrangement of Modules

AU - Atkin, Kate E.

AU - Brentnall, Andrew S.

AU - Harris, Gemma

AU - Bingham, Richard J.

AU - Erat, Michele C.

AU - Millard, Christopher J.

AU - Schwarz-Linek, Ulrich

AU - Staunton, David

AU - Vakonakis, Ioannis

AU - Campbell, Iain D.

AU - Potts, Jennifer R.

PY - 2010/11/19

Y1 - 2010/11/19

N2 - Fibronectin-binding proteins (FnBPs) of Staphylococcus aureus and Streptococcus pyogenes mediate invasion of human endothelial and epithelial cells in a process likely to aid the persistence and/or dissemination of infection. In addition to binding sites for the N-terminal domain (NTD) of fibronectin (Fn), a number of streptococcal FnBPs also contain an upstream region (UR) that is closely associated with an NTD-binding region; UR binds to the adjacent gelatin-binding domain (GBD) of Fn. Previously, UR was shown to be required for efficient streptococcal invasion of epithelial cells. Here we show, using a Streptococcus zooepidemicus FnBP, that the UR-binding site in GBD resides largely in the 8F19F1 module pair. We also show that UR inhibits binding of a peptide from the α1 chain of type I collagen to 8F19F1 and that UR binding to 8F1 is likely to occur through anti-parallel β-zipper formation. Thus, we propose that streptococcal proteins that contain adjacent NTD- and GBD-binding sites form a highly unusual extended tandem β-zipper that spans the two domains and mediates high affinity binding to Fn through a large intermolecular interface. The proximity of the UR- and NTD-binding sequences in streptococcal FnBPs is consistent with a non-linear arrangement of modules in the tertiary structure of the GBD of Fn.

AB - Fibronectin-binding proteins (FnBPs) of Staphylococcus aureus and Streptococcus pyogenes mediate invasion of human endothelial and epithelial cells in a process likely to aid the persistence and/or dissemination of infection. In addition to binding sites for the N-terminal domain (NTD) of fibronectin (Fn), a number of streptococcal FnBPs also contain an upstream region (UR) that is closely associated with an NTD-binding region; UR binds to the adjacent gelatin-binding domain (GBD) of Fn. Previously, UR was shown to be required for efficient streptococcal invasion of epithelial cells. Here we show, using a Streptococcus zooepidemicus FnBP, that the UR-binding site in GBD resides largely in the 8F19F1 module pair. We also show that UR inhibits binding of a peptide from the α1 chain of type I collagen to 8F19F1 and that UR binding to 8F1 is likely to occur through anti-parallel β-zipper formation. Thus, we propose that streptococcal proteins that contain adjacent NTD- and GBD-binding sites form a highly unusual extended tandem β-zipper that spans the two domains and mediates high affinity binding to Fn through a large intermolecular interface. The proximity of the UR- and NTD-binding sequences in streptococcal FnBPs is consistent with a non-linear arrangement of modules in the tertiary structure of the GBD of Fn.

KW - Bacteria

KW - Collagen

KW - Extracellular matrix proteins

KW - Fibronectin

KW - Protein-protein interactions

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