Regulation of the amplification C3 convertase of human complement by an inhibitory protein isolated from human erythrocyte membrane.
An activity that is inhibitory to the properdin-stabilized amplification C3 convertase (C3b,Bb,P) was solubilized from human erythrocyte (E(hu)) membranes by Nonidet P-40 and purified to homogeneity. The inhibitory membrane glycoprotein had an apparent M(r) of 1-1.2x10(6) on gel filtration in the presence of Nonidet P-40. On sodium dodecyl sulfate/polyacrylamide gel electrophoresis it presented a single stained band with an apparent M(r) of 205,000, with or without prior reduction of disulfides. The inhibitory protein of the E(hu) membrane produced a dose-related, first-order decay of C3b,Bb,P function on sheep erythrocytes (E(s)) and released (125)I-labeled Bb from these sites, indicating a mechanism of inhibition by decay-dissociation of the amplification C3 convertase. The 50% inhibitory dose of the E(hu) membrane protein was not altered by removal of sialic acid from the E(s) bearing C3b,Bb,P sites. E(hu) membrane protein also serves as a cofactor for C3b inactivator-induced cleavage of the alpha polypeptide chain of C3b. Thus, the inhibitory membrane protein can abrogate the activity of amplification convertase sites that have formed and also can prevent generation of such sites by augmenting irreversible inactivation of C3b.Discrimination between cells by the alternative complement pathway occurs after initial deposition of C3b and is related to the modulation by surface constituents of the capacity of bound C3b to function as a subunit of the amplification C3 convertase. The existence in the E(hu) membrane of a protein that can impair the functions of membrane-bound C3b and C3b,Bb,P could represent a molecular basis for preventing inappropriate self-recognition.
D001665:Binding Sites; D003166:Complement Activating Enzymes / Q000037:antagonists & inhibitors*; D003167:Complement Activation; D050577:Complement C3-C5 Convertases / Q000037:antagonists & inhibitors*; D003179:Complement C3b / Q000378:metabolism; D003180:Complement C3b Inactivator Proteins / Q000378:metabolism; D011415:Complement Factor B / Q000378:metabolism; D003170:Complement Pathway, Alternative; D004910:Erythrocyte Membrane / Q000276:immunology* / Q000378:metabolism; D004912:Erythrocytes / Q000276:immunology*; D006801:Humans; D007700:Kinetics; D011485:Protein Binding; D012794:Sialic Acids / Q000097:blood / Q000276:immunology
D003180:Complement C3b Inactivator Proteins; D012794:Sialic Acids; D003179:Complement C3b; D003166:Complement Activating Enzymes; D050577:Complement C3-C5 Convertases; D011415:Complement Factor B