Evidence for steric regulation of fibrinogen binding to staphylococcus aureus fibronectin-binding protein A (FnBPA)

Stemberk, Vaclav and Jones, Richard P.O. and Moroz, Olga and Atkin, Kate E. and Edwards, Andrew M. and Turkenburg, Johan P. and Leech, Andrew P. and Massey, Ruth C. and Potts, Jennifer. R. (2014) Evidence for steric regulation of fibrinogen binding to staphylococcus aureus fibronectin-binding protein A (FnBPA). Journal of Biological Chemistry. ISSN 0021-9258

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Background: Staphylococcus aureus fibronectin-binding protein A (FnBPA) binds fibronectin and fibrinogen at adjacent sites. Results: The fibrinogen-binding mechanism is similar but not identical to homologous bacterial proteins. Ternary complex formation by intact fibronectin and fibrinogen on adjacent FnBPA sites could not be demonstrated. Conclusion: Fibrinogen-binding is sterically regulated by fibronectin binding. Significance: Steric regulation might result in targeting of S. aureus to fibrin clots. ABSTRACT The adjacent fibrinogen (Fg)- and fibronectin (Fn)- binding sites on Fn-binding protein A (FnBPA), a cell-surface protein from Staphylococcus aureus, are implicated in the initiation and persistence of infection. FnBPA contains a single Fg-binding site (that also binds elastin) and multiple Fn-binding sites. Here, we solved the structure of the N2N3 domains containing the Fg-binding site of FnBPA in the apo-form and in complex with a Fg-peptide. The Fg-binding mechanism is similar to that of homologous bacterial proteins but without the requirement for “latch” strand residues. We show that the Fg- and the most N-terminal Fn-binding sites are non-overlapping but in close proximity. While Fg and a sub-domain of Fn can form a ternary complex on an FnBPA protein construct containing a Fg- and single Fn-binding site, binding of intact Fn appears to inhibit Fg binding, suggesting steric regulation. Given the concentrations of Fn and Fg in the plasma, this mechanism might result in targeting of S. aureus to fibrin-rich thrombi or elastin-rich tissues.

Item Type: Journal Article
Additional Information: Citation: Stemberk,V., Jones,R.P.O., Moroz,O., Atkin,K.E., Edwards,A.M., Turkenburg,J.P., Leech,A.P., Massey,R.C. and Potts,J.R., 2014. Evidence for Steric Regulation of Fibrinogen Binding to Staphylococcus aureus Fibronectin-binding Protein A (FnBPA). Journal of Biological Chemistry, 289, 2nd May 2014..
Faculty: Faculty of Science & Technology
Depositing User: Mr I Walker
Date Deposited: 16 Jul 2014 13:38
Last Modified: 14 Nov 2016 09:52
URI: http://arro.anglia.ac.uk/id/eprint/323093

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