Third component of complement (C3): structural properties in relation to functions.
The third component of complement (C3) fulfills a pivotal role in the functions of the complement system. We have investigated the topological relationships among its polypeptide chains, physiologic fragments, enzyme attack regions, and functional sites. C3 consists of two chains (alpha and beta) which are linked by disulfide bonds and noncovalent forces and which have molecular weights of, respectively, 120,000 and 75,000. C3 is activated by action of C3 convertase on the alpha-chain. With hydrolysis of one polypeptide bonds, C3a, the 9000 dalton activation peptide is dislocated from the NH2-terminal portion of the alpha-chain. A previously concealed binding region is thereby transiently revealed in the C3b-fragment (181,000 dalton) which displays affinity for apparently nonspecific acceptors present on biological membranes. Binding of nascent C3b membranes occurs through the C3d portion of the fragment because subsequent action of the C3b-inactivator or trypsin on bound C3b causes release of C3c, but not of C3d. Bound C3b and C3d possess stable sites that are capable of binding to specific receptors present on a limited variety of cells. We propose that all known physiologically occurring fragments of C3 arise by enzymatic cleavage of the alpha-chain: C3a, C3b, C3c, and C3d. Whereas C3a (alpha1) and C3e (alpha2) consist of a single chain and C3b consists of two chains (alpha' and beta), C3c is composed of the entire beta-chain and multiple fragments of the alpha-chain, each of which is linked by disulfide bonds to the beta-chain.
D001665:Binding Sites; D002845:Chromatography; D002850:Chromatography, Gel; D003176:Complement C3 / Q000378:metabolism; D003165:Complement System Proteins; D004220:Disulfides; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D006882:Hydroxyapatites; D007104:Immune Adherence Reaction; D007122:Immunoelectrophoresis; D008970:Molecular Weight; D010084:Oxidation-Reduction; D010447:Peptide Hydrolases; D010455:Peptides / Q000302:isolation & purification; D011485:Protein Binding; D012967:Sodium Dodecyl Sulfate; D014357:Trypsin
D003176:Complement C3; D004220:Disulfides; D006882:Hydroxyapatites; D010455:Peptides; D012967:Sodium Dodecyl Sulfate; D003165:Complement System Proteins; D010447:Peptide Hydrolases; D014357:Trypsin