Regions of functional upstream domain of protein F1 of streptococcus pyogenes necessary for exposure of tenth type III module in fibronectin

Abstract

The 49 amino acid portion of the F1 surface protein of Streptococcus pyogenes known as the functional upstream domain (FUD) interacts with Fn in an unknown manner that prevents assembly of a Fn matrix. When FUD binds to Fn, it causes a conformational change that exposes 10-FnIII. This study examined the important regions of FUD that are needed for binding of FUD to Fn by using 18 mutant FUD peptides. A monoclonal antibody (mAb) was used to detect an epitope on 10-FnIII that becomes available upon a conformational change in Fn. Mutant FID peptides that had residues deleted lost their function to expose 10-FnIII. Other mutant FID peptides that had block alanine substitutions had varying abilities to expose 10-FnIII, dependent upon the specific residues that were mutated. Heparin, known to bind to Fn in the same region as FID, can bind to Fn and cause exposure of 10-FnIII, but does not inhibit FUD binding to Fn.