Antiphagocytic activity of streptococcal M protein: selective binding of complement control protein factor H.
Isolated complement components were used to study the regulation of the alternative complement pathway C3 convertase (EC 3.4.21.47), also called C3b,Bb, on M protein-carrying (M+) and M protein-lacking (M-) streptococci. Neither M- nor M+ streptococci directly affected the formation or dissociation of the surface-bound C3b,Bb or the inactivation of surface-bound C3b by factor I. However, the activity of the serum control protein of the alternative complement pathway, factor H, in controlling streptococcus-bound C3b and C3b,Bb was 6-8 times stronger on M+ organisms than on M- organisms. Furthermore, M+ streptococci of different serotypes and purified streptococcal M6 protein were shown to selectively bind factor H, the dissociation constants ranging from 4.5 X 10(-6) M to 6 X 10(-7) M. We conclude that the antiphagocytic activity of streptococcal M protein may be due to complement inhibition mediated by the binding of factor H. Binding of a regulatory protein appears to be a previously unrecognized route by which a pathogen is able to evade alternative pathway activation.
D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins / Q000378:metabolism*; D002352:Carrier Proteins; D003167:Complement Activation; D003179:Complement C3b / Q000378:metabolism; D003180:Complement C3b Inactivator Proteins / Q000378:metabolism*; D011415:Complement Factor B / Q000378:metabolism; D017242:Complement Factor H; D003170:Complement Pathway, Alternative; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D010587:Phagocytosis; D011485:Protein Binding; D013291:Streptococcus / Q000378:metabolism
D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; C493495:CFH protein, human; D002352:Carrier Proteins; D003180:Complement C3b Inactivator Proteins; C014689:streptococcal M protein; D003179:Complement C3b; D017242:Complement Factor H; D011415:Complement Factor B