Biomaterial Database

Initiation of the alternative pathway of complement: recognition of activators by bound C3b and assembly of the entire pathway from six isolated proteins. 1978

R D Schreiber, and M K Pangburn, and P H Lesavre, and H J Müller-Eberhard

An intact alternative pathway of complement activation was assembled from six isolated proteins present at their respective physiological concentrations (C3, 1200 microgram/ml: factor B, 200 microgram/ml; factor D, 2 microgram/ml; beta1H, 560 microgram/ml; C3b inactivator, 34 microgram/ml; and native properdin, 20 microgram/ml). Initiation of the pathway required the presence of five of these proteins not including properdin. The initial C3 convertase of the system was shown to be a fluid-phase rather than a surface-bound enzyme. The ability of the pathway to discriminate between activator and nonactivator was found to reside in the bound C3b molecule. When bound to the surface of an activator through its labile binding site, C3b interacts with surface structures of the activator through another site on the molecule. This interaction results in diminished beta1H binding to C3b and thereby allows the bound C3b molecule to escape control and participate in C3 convertase formation. Thus, initiation of the alternative pathway is a two-step process, the first being non-specific and the second being discriminatory.

UI	MeSH Term	Description	Entries
D011414	Properdin	A 53-kDa protein that is a positive regulator of the alternate pathway of complement activation (COMPLEMENT ACTIVATION PATHWAY, ALTERNATIVE). It stabilizes the ALTERNATIVE PATHWAY C3 CONVERTASE (C3bBb) and protects it from rapid inactivation, thus facilitating the cascade of COMPLEMENT ACTIVATION and the formation of MEMBRANE ATTACK COMPLEX. Individuals with mutation in the PFC gene exhibit properdin deficiency and have a high susceptibility to infections.	Complement Factor P,Factor P, Complement
D011415	Complement Factor B	A glycine-rich, heat-labile serum glycoprotein that contains a component of the C3 CONVERTASE ALTERNATE PATHWAY (C3bBb). Bb, a serine protease, is generated when factor B is cleaved by COMPLEMENT FACTOR D into Ba and Bb.	C3 Proactivator,C3PA,Complement 3 Proactivator,Factor B,Properdin Factor B,Bb Fragment of Factor B,Complement Factor B Fragment, Bb,Complement Factor B, Alternative Pathway,Complement Factor B-Derived Fragment Bb,Complement Factor Ba,Complement Factor Bb,Complement Protein B,Complement Protein Factor B,Properdin Factor Ba,Properdin Factor Bb,Properdin Factor Bf,Properdin Factor Bf F1,Bb, Complement Factor,Complement Factor B Derived Fragment Bb,Factor B, Complement,Factor B, Properdin,Factor Ba, Complement,Factor Ba, Properdin,Factor Bb, Complement,Factor Bb, Properdin,Factor Bf, Properdin,Proactivator, C3,Proactivator, Complement 3,Protein B, Complement
D011416	Complement Factor D	A serum protein which is important in the ALTERNATIVE COMPLEMENT ACTIVATION PATHWAY. This enzyme cleaves the COMPLEMENT C3B-bound COMPLEMENT FACTOR B to form C3bBb which is ALTERNATIVE PATHWAY C3 CONVERTASE.	Adipsin,C3 Convertase Activator,C3PA Convertase,Factor D,Properdin Factor D,28 kDa Protein, Adipocyte,C3 Proactivator Convertase,C3PAse,Complement Protein D,D Component of Complement,GBGase,Proactivator Convertase,Activator, C3 Convertase,Complement D Component,Convertase Activator, C3,Convertase, C3 Proactivator,Convertase, C3PA,Convertase, Proactivator,Factor D, Complement,Factor D, Properdin,Protein D, Complement
D003167	Complement Activation	The sequential activation of serum COMPLEMENT PROTEINS to create the COMPLEMENT MEMBRANE ATTACK COMPLEX. Factors initiating complement activation include ANTIGEN-ANTIBODY COMPLEXES, microbial ANTIGENS, or cell surface POLYSACCHARIDES.	Activation, Complement,Activations, Complement,Complement Activations
D003170	Complement Pathway, Alternative	Complement activation initiated by the interaction of microbial ANTIGENS with COMPLEMENT C3B. When COMPLEMENT FACTOR B binds to the membrane-bound C3b, COMPLEMENT FACTOR D cleaves it to form alternative C3 CONVERTASE (C3BBB) which, stabilized by COMPLEMENT FACTOR P, is able to cleave multiple COMPLEMENT C3 to form alternative C5 CONVERTASE (C3BBB3B) leading to cleavage of COMPLEMENT C5 and the assembly of COMPLEMENT MEMBRANE ATTACK COMPLEX.	Alternative Complement Pathway,Properdin Pathway,Alternative Complement Activation Pathway,Complement Activation Pathway, Alternative
D003179	Complement C3b	The larger fragment generated from the cleavage of COMPLEMENT C3 by C3 CONVERTASE. It is a constituent of the ALTERNATIVE PATHWAY C3 CONVERTASE (C3bBb), and COMPLEMENT C5 CONVERTASES in both the classical (C4b2a3b) and the alternative (C3bBb3b) pathway. C3b participates in IMMUNE ADHERENCE REACTION and enhances PHAGOCYTOSIS. It can be inactivated (iC3b) or cleaved by various proteases to yield fragments such as COMPLEMENT C3C; COMPLEMENT C3D; C3e; C3f; and C3g.	C3b Complement,C3bi,Complement 3b,Complement Component 3b,Inactivated C3b,iC3b,C3b, Complement,C3b, Inactivated,Complement, C3b,Component 3b, Complement
D003180	Complement C3b Inactivator Proteins	Endogenous proteins that inhibit or inactivate COMPLEMENT C3B. They include COMPLEMENT FACTOR H and COMPLEMENT FACTOR I (C3b/C4b inactivator). They cleave or promote the cleavage of C3b into inactive fragments, and thus are important in the down-regulation of COMPLEMENT ACTIVATION and its cytolytic sequence.	C3b Inactivators,C3b Inhibitors,Complement 3b Inactivators,Complement 3b Inhibitors,Complement C3b Inactivators,Complement C3b Inhibitor Proteins,Conglutinogen Activating Factors,Factors, Conglutinogen Activating,Inactivators, C3b,Inactivators, Complement 3b,Inactivators, Complement C3b,Inhibitors, C3b,Inhibitors, Complement 3b
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D001665	Binding Sites	The parts of a macromolecule that directly participate in its specific combination with another molecule.	Combining Site,Binding Site,Combining Sites,Site, Binding,Site, Combining,Sites, Binding,Sites, Combining
D050577	Complement C3-C5 Convertases	Serine proteases that cleave COMPLEMENT C3 into COMPLEMENT C3A and COMPLEMENT C3B, or cleave COMPLEMENT C5 into COMPLEMENT C5A and COMPLEMENT C5B. These include the different forms of C3/C5 convertases in the classical and the alternative pathways of COMPLEMENT ACTIVATION. Both cleavages take place at the C-terminal of an ARGININE residue.	C3 Convertase,C 3 Convertase,C3 Activator,C3-C5 Convertase,C5 Cleaving Enzyme,C5 Convertase,Complement 3 Convertase,Complement 5 Convertase,Complement C3 Convertases,Complement C5 Convertases,Activator, C3,C3 C5 Convertase,C3 Convertases, Complement,C3-C5 Convertases, Complement,C5 Convertases, Complement,Complement C3 C5 Convertases,Convertase, C 3,Convertase, C3,Convertase, C3-C5,Convertase, Complement 3,Convertases, Complement C3,Convertases, Complement C3-C5,Convertases, Complement C5