CALCIUM-LINKED SELF-ASSOCIATION OF HUMAN-COMPLEMENT C1(S-)

The weight-average molecular weight of C1sBAR, an activated serine protease subcomponent of human complement C1, has been measured by means of sedimentation equilibrium over a wide range of both protein and calcium ion concentrations. The combined data may be accounted for quantitatively by a simple model for Ca2+-dependent self-association of C1sBAR to a dimer. According to this model, the monomer contains a single Ca2+ binding site with K congruent-to 3 X 10(5) M-1, and the dimer contains three independent Ca binding sites, two having a Ca2+ affinity lower than that of the monomer (K congruent-to 3 X 10(4) M-1). The third binding site in the dimer, which presumably lies at the interface between the two amino-terminal alpha domains, has a higher Ca2+ affinity (K congruent-to 1 X 10(8) M-1) and provides the driving force for C1sBAR dimerization in the presence of calcium.