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Metallica One

The binding of C1 to antigen-antibody complexes that contain immunoglobulin M (IgM) or immunoglobulin G (IgG) antibodies (subclasses IgG1, IgG2, and IgG3) activates the classical pathway. Only these Ig isotypes have complement-binding sites in the Fc portion (CH2 domain of IgG and CH3 domain of IgM). C1 is a large multimeric protein complex composed of 3 subunits: C1q, C1r, and C1s. C1r and C1s are serine esterases. The C1q must bind to the 2 Fc portions of immunoglobulin (Ig) heavy chains to initiate the complement cascade. The binding of C1q to the immune complex leads to enzymatic activation of C1r, which, in turn, cleaves and activates C1s. Activated C1s cleaves C4 into C4a and C4b. A single activated C1s can cleave numerous molecules of C4. This process leads to continuous formation of C4b but is inhibited by C1 esterase inhibitor enzyme (C1INH). Deficiency of C1INH leads to uninhibited formation of C4b and C4a. C4b has an internal thioester bond that allows C4b to fo

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