Abstract

The interaction between Staphylococcus aureus and Streptococcus pyogenes with the human plasma and extracellular matrix protein fibronectin triggers bacterial invasion of host cells. This process has been proposed to aid haematogenous dissemination of infection and evasion of the host immune system. We have used a range of biophysical techniques to define the binding sites in the host and bacterial proteins and the structure of the complex that forms. In a highly unusual mechanism of protein-protein recognition, the bacterial peptide undergoes a transition from an intrinsically disordered state, to an extended anti-parallel β-strand along the triple-stranded β-sheets of up to five sequential fibronectin modules (1-3). A dissection of the S. aureus and S. pyogenes fibronectin-binding proteins, based on the tandem β-zipper and confirmed using isothermal titration calorimetry, has identified multiple high affinity binding sites in both proteins (4,5). In a separate project, we have been investigating a redox-sensing anti-sigma factor (RsrA) from Streptomyces coelicolor. We have determined the solution structures of the reduced and oxidized forms of RsrA. Comparison with the structures of homologous anti-sigma factors in complex with their cognate sigma factors suggests another unusual mechanism of protein-protein recognition.

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