The streptococcal binding site in the gelatin-binding domain of fibronectin is consistent with a non-linear arrangement of modules.

Journal article

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 (8)F1(9)F1 module pair. We also show that UR inhibits binding of a peptide from the α1 chain of type I collagen to (8)F1(9)F1 and that UR binding to (8)F1 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.

Authors: Atkin, K; Brentnall, A; Harris, G; Bingham, R; Erat, M

• Publication status: Published
• Journal: Journal of biological chemistry
• Volume: 285
• Issue: 47
• Pages: 36977-36983
• Publication date: 2010-11-01
• DOI: 10.1074/jbc.m110.156935
• EISSN: 1083-351X
• ISSN: 0021-9258
• Language: English
• Keywords: Gelatin; Molecular Sequence Data; Humans; Protein Binding; Recombinant Proteins; Crystallography, X-Ray; Protein Structure, Tertiary; Magnetic Resonance Spectroscopy; Binding Sites; Sequence Homology, Amino Acid; Fibronectins; Protein Conformation; Amino Acid Sequence; Streptococcus equi; Models, Molecular