A common theme in interaction of bacterial immunoglobulin-binding proteins with immunoglobulins illustrated in the equine system.
The M protein of Streptococcus equi subsp. equi known as fibrinogen-binding protein (FgBP) is a cell wall-associated protein with antiphagocytic activity that binds IgG. Recombinant versions of the seven equine IgG subclasses were used to investigate the subclass specificity of FgBP. FgBP bound predominantly to equine IgG4 and IgG7, with little or no binding to the other subclasses. Competitive binding experiments revealed that FgBP could inhibit the binding of staphylococcal protein A and streptococcal protein G to both IgG4 and IgG7, implicating the Fc interdomain region in binding to FgBP. To identify which of the two IgG Fc domains contributed to the interaction with FgBP, we tested two human IgG1/IgA1 domain swap mutants and found that both domains are required for full binding, with the CH3 domain playing a critical role. The binding site for FgBP was further localized using recombinant equine IgG7 antibodies with single or double point mutations to residues lying at the CH2-CH3 interface. We found that interaction of FgBP with equine IgG4 and IgG7 was able to disrupt C1q binding and antibody-mediated activation of the classical complement pathway, demonstrating an effective means by which S. equi may evade the immune response. The mode of interaction of FgBP with IgG fits a common theme for bacterial Ig-binding proteins. Remarkably, for those interactions studied in detail, it emerges that all the Ig-binding proteins target the CH2-CH3 domain interface, regardless of specificity for IgG or IgA, streptococcal or staphylococcal origin, or host species (equine or human).
Lewis
Melanie J
MJ
Division of Pathology and Neuroscience, University of Dundee Medical School, Ninewells Hospital, Dundee DD19SY, United Kingdom.
Meehan
Mary
M
Owen
Peter
P
Woof
Jenny M
JM
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000737:chemistry; D001426:Bacterial Proteins / Q000737:chemistry*; D006736:Horses; D006801:Humans; D007070:Immunoglobulin A / Q000737:chemistry; D007074:Immunoglobulin G / Q000737:chemistry; D007136:Immunoglobulins / Q000737:chemistry*; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000737:chemistry; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D013210:Staphylococcus / Q000378:metabolism; D013291:Streptococcus / Q000378:metabolism
D000906:Antibodies; D001426:Bacterial Proteins; C034284:IgG Fc-binding protein, Streptococcus; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007136:Immunoglobulins; D011994:Recombinant Proteins