title: Identification of the IgA-binding region in streptococcal protein Arp.
abstract: Cell surface proteins that bind to the Fc part of human IgA are expressed by different species of pathogenic streptococci. The most extensively characterized streptococcal IgA-binding protein is the Streptococcus pyogenes protein Arp4, a member of the M protein family. Here we describe work that identifies the IgA-binding region in this streptococcal protein. A comparison of the amino acid sequences of protein Arp4 and four other IgA-binding proteins of S. pyogenes first made possible the identification of a putative IgA-binding region. Site-specific mutagenesis and generation of deletions were then used to show that Arp4 derivatives lacking different parts of the putative IgA-binding region had lost the ability to bind IgA. Conclusive evidence for the localization of the IgA-binding region was obtained through the characterization of a chimeric protein, in which the putative IgA-binding region of Arp4 had been introduced into another S. pyogenes cell surface protein that does not bind IgA. Our data show that a region comprising 29-amino acid residues in the N-terminal part of Arp4 is necessary and sufficient for IgA-binding capacity. Competitive inhibition experiments with synthetic peptides indicated that the C-terminal half of this 29 residue region may be most important for the IgA-binding property of Arp4. These results identify, for the first time, the ligand-binding region in an Fc alpha binding protein.
authors.affiliation: Department of Microbiology, Lund University, Sweden.
authors.forename: E
authors.initials: E
authors.lastname: Johnsson
authors.forename: G
authors.initials: G
authors.lastname: Andersson
authors.forename: G
authors.initials: G
authors.lastname: Lindahl
authors.forename: L O
authors.initials: LO
authors.lastname: Hedén
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry*; D001665:Binding Sites; D001667:Binding, Competitive; D002352:Carrier Proteins / Q000737:chemistry*; D007070:Immunoglobulin A / Q000378:metabolism*; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010455:Peptides / Q000737:chemistry; D011485:Protein Binding; D011993:Recombinant Fusion Proteins; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013297:Streptococcus pyogenes / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: C062462:Arp4 protein, Streptococcus pyogenes; D001426:Bacterial Proteins; D002352:Carrier Proteins; D007070:Immunoglobulin A; D010455:Peptides; D011993:Recombinant Fusion Proteins