Classical Complement Pathway - C1 and Its Subunits

C1 and Its Subunits

This initial enzyme, C1, is a complex formed through a calcium-dependent association between two reversibly interacting subunits, C1q and C1 (C1qr2s2). Approximately 70% of C1 is at all times present in this complex form. C1 occurs in serum as a proenzyme that tends to undergo autoactivation but is strictly controlled by C1-inhibitor (C1-In or C1 esterase). Upon the binding of C1 to immune complexes by virtue of the affinity of C1q for immunoglobulins (to be specific, IgM and IgG), the controlling action of C1-In is overcome, and C1q effects activation of C1r2s2.

C1q possesses no intrinsic catalytic activity, but, when any of several activators bind to the C1q subcomponent of C1, the homologous C1r and C1s subcomponents are converted into catalytically active species, namely C1r* and C1s*, triggering the first step of the classical pathway of complement activation.

Thus, on binding to immune complexes through C1q, the subunits of C1 become firmly associated and autoactivation commences even in the presence of the Cl-In.