Autoactivation of human complement subcomponent C1r involves structural changes reflected in modifications of intrinsic fluorescence, circular dichroism and reactivity with monoclonal antibodies.

Autoactivation of C1r is closely correlated with an irreversible increase of its intrinsic fluorescence. The activation and the fluorescence increase of C1r are accelerated on addition of activated C1r. Ca2+, di-isopropyl phosphorofluoridate and C1 inhibitor, which all inhibit, although to different extents, C1r activation, inhibit in parallel the fluorescence increase. C1r activation is blocked at pH 4.0-5.0, whereas it is accelerated at pH 10.5; under the same conditions the fluorescence increase shows parallel effects. No such fluorescence increase is observed during C1s activation by trace amounts of C1r. Far-u.v. circular-dichroism spectra of C1r indicate 73 and 78% of unordered form in both the proenzyme and the activated species respectively. The slight changes observed on activation are not restricted to C1r, as comparable results are obtained for proenzyme and activated C1s. C1r activation appears thus to involve structural changes leading to an 'activated state' distinct from the 'proenzyme state'. Monoclonal antibody to activated C1r is poorly reactive with proenzyme C1r, a finding that also supports this hypothesis.