Atkin, Kate E, Brentnall, Andrew S, Harris, Gemma, Bingham, Richard, Erat, Michele C, Millard, Christopher J, Schwarz-Linek, Ulrich, Staunton, David, Vakonakis, Ioannis, Campbell, Iain D and Potts, Jennifer R (2010) The streptococcal binding site in the gelatin-binding domain of fibronectin is consistent with a non-linear arrangement of modules. The Journal of biological chemistry, 285 (47). pp. 36977-83. ISSN 1083-351X
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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.
|Subjects:||Q Science > Q Science (General)|
Q Science > QH Natural history > QH301 Biology
|Schools:||School of Applied Sciences|
School of Applied Sciences > Biomolecular Sciences Research Centre
|Depositing User:||Richard Bingham|
|Date Deposited:||05 Apr 2011 14:07|
|Last Modified:||15 Jun 2011 12:03|
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