Subunit interactions in the first component of complement, C1

Abstract

Interactions between C1q and other subunits of C1 were analyzed by sucrose gradient ultracentrifugation. A zone of dilute, radioiodine labelled C1q was sedimented through uniform concentrations of either C1r 2C1s 2, C1r 2, C1r 2 or C1s (2) . The dissociation constants were found to be 3×10 −9M and 6×10 −9M for C1r 2C1s 2 and C1r 2 binding respectively. Hill coefficients of 1 indicated no cooperativity in these bindings. Positive cooperativity was found in binding of C1s to C1q. Dissociation constants of 2×10 −6M and 5×10 −8M were obtained from computer modelling of a two step binding mechanism. No inter-action was detected between C1q and activated C1r 2 . The data indicate that most of the interactions between C1q and C1r 2C1s 2 originates from a strong binding to the C1r 2 moiety of the zymogen complex. This interaction is lost upon activation of C1r 2.