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

Abstract

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.

Binding of IgA and/or IgG is a common property among clinical isolates of group A streptococci

“…In addition to these well-studied proteins, some strains of group A streptococci are also known to express a cell-surface receptor with affinity for the Fc part of IgA or IgG [5][6][7][8]. The structure and binding properties of such immunoglobulin receptors has now been studied in considerable detail, but it has not yet been possible to define their biological role, although the available evidence suggests that they are virulence factors, like the M proteins [9,10]. Information concerning the expression of the immunoglobulin receptors by routine clinical isolates of group A streptococci is also limited.…”

Isolated Hypervariable Regions Derived from Streptococcal M Proteins Specifically Bind Human C4b-Binding Protein: Implications for Antigenic Variation

“…The 51-residue M2-N peptide corresponds to residues 1-48 of the M2 (ML2.1) protein (17), with a Tyr-Tyr-Cys sequence added. The 47-residue M4-N peptide corresponds to residues 1-45 of the M4 (Arp4) protein (16), with a Tyr-Cys sequence added. Due to technical difficulties in synthesizing peptides containing both arginine and tryptophan, the arginine (32) residue in the M4 protein was replaced with a lysine residue in the M4-N peptide.…”

“…The full-length streptococcal M4 (Arp4), M5, and M22 (Sir22) proteins were purified as described, after expression of the cloned gene in Escherichia coli (11,16,19).…”

Immunological Recognition of Fibronectin‐Binding Proteins of Staphylococcus aureus and Staphylococcus capitis, Strain LK499

“…The consensus sequence, LPXTGX, is reported to be in cell-wall proteins of several gram positive bacteria (4,5,7,11,12,25,30). It may be necessary for an anchoring of M protein on the streptococcal cell wall and a released form of this protein seems to have a part of this consensus sequence at the C-terminus (7,12,23). FnBPs of S. aureus may be released in a similar manner with an endogeneous enzyme on bacterial membrane as reported for M protein (24).…”