The Streptococcal Binding Site in the Gelatin-binding Domain of Fibronectin Is Consistent with a Non-linear Arrangement of Modules |
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Authors: | 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 |
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Affiliation: | From the Departments of ‡Biology and ;‖Chemistry, University of York, Heslington, York, YO10 5DD, United Kingdom, ;the §Department of Biochemistry, University of Oxford, Oxford OX1 3QU, United Kingdom, and ;the ¶Centre for Biomolecular Sciences, University of St. Andrews, North Haugh, St. Andrews, Fife KY16 9ST, Scotland, United Kingdom |
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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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Keywords: | Bacteria Collagen Extracellular Matrix Proteins Fibronectin Protein-Protein Interactions |
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