Duplication of a DNA sequence homologous to genes for immunoglobulin receptors and M proteins in Streptococcus pyogenes.

The nucleotide sequence of an open reading frame of 355 amino acids downstream of the IgA-binding protein gene arp4 in Streptococcus pyogenes M-type 4 has been determined. Analysis of the deduced amino acid sequence for the open reading frame shows an extensive homology to streptococcal M proteins and immunoglobulin binding proteins. Expression of the open reading frame has not been detected and the function may be as a genetic reservoir in the generation of new immunoglobulin receptors and antigenic variants of M proteins.

Molecular characterization of an IgA receptor from group B streptococci: sequence of the gene, identification of a proline-rich region with unique structure and isolation of N-terminal fragments with IgA-binding capacity.

Certain strains of group B streptococci express a cell surface protein that binds IgA and acts as a virulence factor. This IgA receptor is referred to here as protein Bac. The gene for protein Bac was cloned and expressed in Escherichia coli, and the complete nucleotide sequence was determined. The deduced amino acid sequence of 1134 residues includes a signal sequence of 37 amino acids and a putative membrane anchor region at the C-terminal end. The processed form of the receptor, 1097 residues, has a calculated molecular weight of 123,786. There are no cysteines in protein Bac, suggesting a fibrillar structure. The C-terminal half of the protein includes a 90 residues long region with a novel type of periodic structure, the "XPZ motif", in which every third amino acid is proline. Unlike other bacterial immunoglobulin-binding proteins, there are no long repeats in protein Bac. Clones which express only part of the protein Bac gene were used to show that IgA-binding takes place in the N-terminal part of the molecule. Protein Bac was originally described as an antigen called beta, but N-terminal fragments that bind IgA do not react with a reference serum against the beta antigen. These and other data indicate that protein Bac can be divided into two regions with different functions: an N-terminal IgA-binding region and a C-terminal region corresponding to the beta antigen. The IgA-binding region of protein Bac does not show any homology to protein Arp, the IgA receptor from group A streptococci, although these receptors have similar binding properties. This indicates that convergent evolution has favored the appearance of these two structurally different streptococcal IgA receptors.

Extensive sequence homology between IgA receptor and M proteins in Streptococcus pyogenes.

Many strains of Streptococcus pyogenes are known to express a receptor for IgA. The complete nucleotide sequence of the gene for such a receptor, protein Arp4, has been determined. The deduced amino acid sequence of 386 residues includes a signal sequence of 41 amino acids and a putative membrane anchor region, both of which are homologous to similar regions in other streptococcal surface proteins. The processed form of the IgA receptor has a length of 345 amino acids and a calculated molecular weight of 39544. The N-terminal sequence of the processed form is different from that previously found for a similar IgA receptor isolated from a S. pyogenes strain of type M60. The sequence of protein Arp4 shows extensive homology to the C-terminal half of streptococcal M proteins, but not to the streptococcal IgG receptor protein G or staphlyococcal protein A. Apart from the membrane anchor, this homology includes a sequence of 119 amino acid residues containing three repeated units and a 54-residue sequence without repeats. The protein expressed in Escherichia coli is found in the periplasmic space, in which it constitutes the major protein. Protein Arp4 is the first example of a surface protein that has both immunoglobulin-binding capacity and structural features characteristic of M proteins.