Complement C1r-C1s complex (C1r-C1s)

The Complement C1r-C1s complex is a calcium-dependent tetrameric assembly (C1r2s2) that serves as the catalytic core of the C1 complex in the classical complement pathway (UniProt P00736, P09871). Upon binding of the C1q subcomponent to immune complexes or other activators, the zymogen C1r undergoes autoactivation and subsequently cleaves and activates C1s (Gaboriaud et al., 2014, PMID: 24711612). Activated C1s, a serine protease, then cleaves complement components C4 and C2 to form the C3 convertase, propagating the complement cascade (StatPearls, 2023). Dysregulation or overactivation of this complex is implicated in various autoimmune and inflammatory disorders, such as Cold Agglutinin Disease and Systemic Lupus Erythematosus (PubMed, 32810055). Therapeutic strategies, such as the monoclonal antibody Sutimlimab, focus on inhibiting the enzymatic activity of C1s to prevent downstream complement-mediated hemolysis and tissue damage (FDA, 2022).

Other names

C1r2s2 complexComplement C1r-C1s tetramerC1 esteraseComplement component 1 subcomponent r and s complexC1r-C1s complex

Inhibition of the serine protease activity of C1s or C1r to prevent the cleavage of C4 and C2, thereby halting the classical complement cascade (FDA, 2022; StatPearls, 2023).