The Fc binding site for streptococcal protein G is in the C gamma 2-C gamma 3 interface region of IgG and is related to the sites that bind staphylococcal protein A and human rheumatoid factors.
The isolated 35 kDa fragment of protein G obtained by papain digestion of group G streptococci was found to bind solid phase intact IgG, Fc (2C gamma 2 + 2C gamma 3 domains), F(ab')2 and F(acb)2 (F(ab')2 + 2C gamma 2 domains) fragments but not pFc' (2C gamma 3 domains) fragments. The level of binding to rabbit F(acb)2 and rabbit F(ab')2 fragments was similar. Protein G binding to solid phase Fc fragments was inhibited by IgG, Fc, staphylococcal protein A and its monovalent fragment D, but was enhanced by F(ab')2 fragments. Chemical modification of tyrosine but not histidine residues of IgG abrogated its ability to inhibit the binding of protein G to solid phase Fc fragments. Protein G was found to strongly inhibit the binding of a monoclonal and a polyclonal human rheumatoid factor to IgG. These findings indicate that protein G binds with separate sites to the Fc and F(ab')2 fragments of IgG, that the interaction with the Fc fragment occurs at the C gamma 2-C gamma 3 domain interface region and that tyrosine but not histidine residues in this area are likely involved. The relationship of the Fc fragment-binding site specificity of protein G to that of other microbial IgG binding proteins and human rheumatoid factors is discussed.
Stone
G C
GC
Department of Medicine, University of Washington, Seattle 98195.
Sjöbring
U
U
Björck
L
L
Sjöquist
J
J
Barber
C V
CV
Nardella
F A
FA
D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism* / Q000494:pharmacology; D001666:Binding Sites, Antibody; D001667:Binding, Competitive; D006801:Humans; D007127:Immunoglobulin Constant Regions / Q000378:metabolism*; D007128:Immunoglobulin Fragments / Q000378:metabolism; D007074:Immunoglobulin G / Q000378:metabolism*; D007075:Immunoglobulin M / Q000378:metabolism; D007457:Iodine Radioisotopes / Q000378:metabolism; D007700:Kinetics; D008970:Molecular Weight; D011817:Rabbits; D011961:Receptors, Fc / Q000032:analysis* / Q000378:metabolism; D012217:Rheumatoid Factor / Q000378:metabolism*; D013205:Staphylococcal Protein A / Q000378:metabolism*
D001426:Bacterial Proteins; C034284:IgG Fc-binding protein, Streptococcus; D007127:Immunoglobulin Constant Regions; D007128:Immunoglobulin Fragments; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007457:Iodine Radioisotopes; D011961:Receptors, Fc; D013205:Staphylococcal Protein A; D012217:Rheumatoid Factor