Binding of the eighth component of human complement to the soluble cytolytic complex is mediated by its beta subunit.

The noncovalently associated alpha-gamma and beta subunits of the eighth component of human complement (C8) were isolated and examined for their ability to recombine to form C8. Each subunit was also examined to determine its capability to interact independently with the C8 binding site on the soluble form of the cytolytic complex of complement. Results indicate that alpha-gamma and beta physically recombine in solution to form native C8 when mixed in equimolar amounts, a finding consistent with the concomitant appearance of C8 hemolytic activity. The ability of each subunit to interact independently with SC5b-7, the precursor of the soluble cytolytic complex which binds C8, was determined by sucrose density gradient analyses. It was found that alpha-gamma exhibits little affinity for SC5b-7, while the beta subunit readily binds to yield a stable complex of SC5b-7(beta). Interaction of beta was specific for the C8 binding site on SC5b-7 as evidenced by the ability to compete with C8. Results indicate that structural domains which mediate specific interaction of C8 with the nascent cytolytic complex are located in the beta subunit of this unusual protein.