Complement C1s serine protease; Complement C1r serine protease (C1s; C1r)

Complement C1s and C1r serine proteases are modular enzymes that form part of the C1 complex at the apex of the classical complement pathway[1][2][3][4][5]. Each protease contains multiple structural domains: two N-terminal CUB domains, an EGF-like domain, two complement control protein (CCP) modules, and a C-terminal serine protease domain[1][3][4][5]. Upon recognition of antibody-antigen complexes or pathogen surfaces by the C1q recognition subunit, two copies of C1r and C1s assemble into a tetramer and are activated via conformational rearrangement. C1r acts as an initiator protease, autoactivating and then cleaving C1s to activate it. Activated C1s then cleaves complement proteins C4 and C2, which propagates the cascade leading to opsonization, inflammation, and pathogen lysis[1][3][4][5]. These proteases share structural motifs and activation mechanisms with other complement pathway serine proteases, such as MASPs (mannan-binding lectin-associated serine proteases)[5]. Dysfunction or dysregulation of C1s/C1r or their inhibitors (e.g., C1-inhibitor) is implicated in immunological disorders, notably hereditary angioedema, and may contribute to other inflammatory and autoimmune diseases.

Other names

Complement component 1 subcomponent s (C1s)Complement component 1 subcomponent r (C1r)C1s esteraseC1r esterase

Protease inhibition: block serine protease activity to prevent complement activation; C1-inhibitor therapies: prevent overactivation of classical complement pathway, stabilize C1 complex