A study on the structure and interactions of the C1 sub-components C1r and C1s in the fluid phase.
1. Both proenzyme and activated C1r, which are dimers at pH 7.4, dissociated into monomers at pH 5.0 (C1r) and 4.0 (C1r), as shown by the decrease of apparent molecular weight and of sedimentation coefficient, which was shifted from 7.1 S (dimer) to 5.0 S (monomer). 125I-labelling of C1r in the presence of lactoperoxidase occurred, for the dimer, 16-20% in the A chain and 80-84% in the B chain, whereas the distribution was 67.5% and 32.5%, respectively, for the monomer. It appears likely that the two monomers of C1r interact through their A chain and that the A and B chains are relatively independent from each other. 2. 125I-labelling of C1s in the presence of lactoperoxidase confirmed the calcium-dependent dimerization of this subcomponent. In the monomer, the B chain appears to be embedded in the A chain, as shown by the 125I- distribution in these chains, which was 5% and 95%, respectively. This changed after dimerization to 25% and 75%, respectively, which suggests that interactions occur through the A chain of each monomer and lead to an unfolding of the B chain. 3. C1r dimer and C1s monomer were found to interact in the absence of calcium to form a C1r2-C1s complex (7.7 S), whereas in the presence of calcium the two sub-components were associated into a C1r2-C1s2 complex (8.7S). It appears likely that the formation of this tetrameric complex involves both calcium-dependent, and calcium-independent binding forces, and that C1r and C1s interact through their respective A chain which, in the case of C1s, is hidden upon association.
D002118:Calcium / Q000378:metabolism; D055598:Chemical Phenomena; D002621:Chemistry; D003172:Complement C1; D004792:Enzyme Precursors / Q000378:metabolism; D006801:Humans; D007457:Iodine Radioisotopes; D008954:Models, Biological; D010446:Peptide Fragments / Q000378:metabolism; D011487:Protein Conformation
D003172:Complement C1; D004792:Enzyme Precursors; D007457:Iodine Radioisotopes; D010446:Peptide Fragments; D002118:Calcium