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Evidence for Steric Regulation of Fibrinogen binding to Staphylococcus aureus fibronectin-binding protein A (FnBPA).

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JournalJournal of Biological Chemistry
DateE-pub ahead of print - 13 Mar 2014
DatePublished (current) - 2 May 2014
Issue number18
Volume289
Number of pages10
Pages (from-to)12842-12851
Early online date13/03/14
Original languageEnglish

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.

    Research areas

  • Fibrinogen, Fibronectin, Isothermal titration calorimetry, Staphylococcus aureus, Surface Plasmon Resonance (SPR), X-ray crystallography, FnBPA

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