IDENTIFICATION OF THE IGA-BINDING REGION IN STREPTOCOCCAL PROTEIN ARP

Cell surface proteins that bind to the Fc part of human IgA are expres sed by different species of pathogenic streptococci. The most extensiv ely characterized streptococcal IgA-binding protein is the Streptococc us pyogenes protein Arp4, a member of the M protein family. Here we de scribe work that identifies the IgA-binding region in this streptococc al protein. A comparison of the amino acid sequences of protein Arp4 a nd four other IgA-binding proteins of S. pyogenes first made possible the identification of a putative IgA-binding region. Site-specific mut agenesis 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 localiz ation of the IgA-binding region was obtained through the characterizat ion of a chimeric protein, in which the putative IgA-binding region of Arp4 had been introduced into another S. pyogenes cell surface protei n that does not bind IgA. Our data show that a region comprising 29-am ino acid residues in the N-terminal part of Arp4 is necessary and suff icient for IgA-binding capacity. Competitive inhibition experiments wi th synthetic peptides indicated that the C-terminal half of this 29 re sidue region may be most important for the IgA-binding property of Arp 4. These results identify, for the first time, the ligand-binding regi on in an Fc alpha binding protein.