title: Structure of a group C streptococcal protein that binds to fibrinogen, albumin and immunoglobulin G via overlapping modules.
abstract: Pathogenic streptococci express surface proteins that bind to host serum proteins. A novel multiple-ligand-binding protein has now been identified in a species belonging to serotype C streptococci. This protein binds to fibrinogen, albumin and IgG and was therefore designated FAI protein. The structure of the fai gene has been determined, and deletion analysis and expression of FAI fusion polypeptides revealed that the binding domain for fibrinogen and IgG is located within the nonrepetitive N-terminal half of the protein. A 93-amino acid peptide retained the ability to bind both proteins, whereas a 56-amino acid subpeptide only bound fibrinogen. IgG-binding activity required the complete fibrinogen-binding domain and an additional 37 amino acids C-terminal to it, and albumin-binding activity was only obtained with a polypeptide reflecting the complete surface-exposed region of FAI protein indicating that the binding sites for each ligand were located on overlapping modules. Signal sequence, C repeat region and C-terminus revealed high homology to group A streptococcal M proteins whereas the N-terminal region containing the fibrinogen/IgG-binding domains is completely different and exhibits no similarity to any other previously characterized protein. Thus FAI protein exhibits a framework structure that might have evolved in group C streptococci via fusion of unrelated sequences, thereby generating an albumin-binding domain in the functional context of multiple-ligand-binding activity.
authors.affiliation: Department of Microbiology, Technical University Braunschweig/GBF-National Research Centre for Biotechnology, Germany.
authors.forename: S R
authors.initials: SR
authors.lastname: Talay
authors.forename: M P
authors.initials: MP
authors.lastname: Grammel
authors.forename: G S
authors.initials: GS
authors.lastname: Chhatwal
mesh_terms: D000418:Albumins / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D001665:Binding Sites; D017931:DNA Primers / Q000235:genetics; D004269:DNA, Bacterial / Q000235:genetics; D005340:Fibrinogen / Q000378:metabolism; D005798:Genes, Bacterial; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D015394:Molecular Structure; D011485:Protein Binding; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013291:Streptococcus / Q000737:chemistry* / Q000145:classification / Q000235:genetics; D013297:Streptococcus pyogenes / Q000235:genetics
chemical_list: D000418:Albumins; D001426:Bacterial Proteins; D017931:DNA Primers; D004269:DNA, Bacterial; D007074:Immunoglobulin G; D011993:Recombinant Fusion Proteins; D005340:Fibrinogen