Staphylococcus aureus fibronectin‐binding proteins (FnBPs)

Abstract

Polyclonal antibodies against recombinant fibronectin‐binding proteins (gal‐FnBP A and ZZ‐FnBP B) of Staphylococcus aureus were analyzed by both solid‐phase and solution‐phase methods. These antibodies were found to bind homologous antigen and to cross‐react with heterologous antigen. It was also found that antibodies recognize native FnBP on the cell surface. It has been shown, by the inhibition assay, that the majority of antibodies recognize a fibronectin‐binding D1‐D2 sequence of FnBP A. Anti‐FnBP A Fab fails to bind the D3 sequence, though this peptide used in a solution inhibits binding of fibronectin to immobilized FnBP A, similarly to Dl and D2 peptides. Since the anti‐FnBP A antibodies are able to block fibronectin binding to staphylococci by about 50%, it is reasonable to assume that the bacterial receptor has additional binding sites outside the D domain.

Structural and Dynamical Characterization of a Biologically Active Unfolded Fibronectin-Binding Protein from Staphylococcus aureus

“…In addition the unfolded nature of D1-D4 may be an important feature enabling avoidance of the immune system; in an ensemble of highly disordered molecules too few individual interactions may be made with antibody molecules for tight binding to be present overall. The significance of this is supported by previous experimental results that show that blocking antibodies produced against various forms of the D1-D4 immunogen have been found to be largely ineffective (11,(94)(95)(96). In light of these advantages of having an unfolded conformation, it is interesting that a number of other proteins involved in protein-protein interactions such as microtubule-associated protein (97), tau protein (98), the cyclin-dependent kinase inhibitor p21 Waf1/Cip1/Sdi1 (93), the transcriptional activation domain of the herpes virus protein VP16 (99, 100), the non-Aβ component precursor (101), and the inhibitor of flagellum specific sigma factor σ 28 (102) have also been found to be essentially unfolded.…”