Complement C3 convertase: cell surface restriction of beta1H control and generation of restriction on neuraminidase-treated cells.
The alternative or properdin pathway of complement is primarily controlled by the endopeptidase C3b inactivator (C3bINA) and the nonproteolytic glycoprotein beta1H. The molecular mechanisms of control were investigated by performing binding studies of radiolabeled complement proteins to C3b bearing sheep erythrocytes (E(S)C3b). C3b was found to have distinct binding sites for beta1H, C3bINA, Factor B, and properdin. beta1H binding increased C3bINA binding 30-fold, while Factor B binding prevented C3bINA action on C3b and was competitive with beta1H binding. Properdin binding, which facilitates Factor B interaction with C3b, had no effect on the beta1H and C3bINA sites. Activators such as rabbit erythrocytes (E(R)) have previously been shown to interfere with the effectiveness of the control by C3bINA and beta1H, thereby allowing unrestricted formation of C3 convertase. Such restriction of control does not occur on the surface of E(S), a nonactivator of the alternative pathway. On the basis of comparative binding studies, restriction of control is explained entirely by reduced binding of beta1H to E(R)C3b relative to E(S)C3b. Access of properdin, Factor B, C3bINA, and the Fab fragment of anti-C3 to the two cell types was unrestricted. Restriction of beta1H control could be generated on the surface of E(S) by removal of cell-surface sialic acid with neuraminidase (acylneuraminyl hydrolase; EC 3.2.1.18). This enzymatic treatment converted E(S) from a nonactivator to an activator of the alternative pathway.
D001665:Binding Sites; D001667:Binding, Competitive; D003166:Complement Activating Enzymes / Q000378:metabolism*; D003176:Complement C3 / Q000378:metabolism*; D050577:Complement C3-C5 Convertases / Q000378:metabolism*; D003180:Complement C3b Inactivator Proteins / Q000378:metabolism; D011415:Complement Factor B / Q000378:metabolism*; D004792:Enzyme Precursors / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism*; D007140:Immunoglobulin Fab Fragments; D009439:Neuraminidase / Q000378:metabolism; D011414:Properdin / Q000378:metabolism*
D003176:Complement C3; D003180:Complement C3b Inactivator Proteins; D004792:Enzyme Precursors; D006023:Glycoproteins; D007140:Immunoglobulin Fab Fragments; D011414:Properdin; D003166:Complement Activating Enzymes; D009439:Neuraminidase; D050577:Complement C3-C5 Convertases; D011415:Complement Factor B