Complement C1 enzyme complex (C1 complex)

The Complement C1 enzyme complex is a large, multi-protein assembly that initiates the classical pathway of the complement system, a critical component of innate immunity (StatPearls, Physiology, Complement Cascade). It consists of the recognition protein C1q and a tetramer of two serine proteases, C1r and C1s (UniProt P09871, P00736). Activation is typically triggered by the binding of C1q to antigen-antibody complexes (IgG or IgM) or specific pathogen surfaces, leading to the sequential autoactivation of C1r and subsequent activation of C1s (NCBI, Molecular Immunology, 2015). The activated C1s subunit then cleaves complement components C4 and C2, facilitating the formation of the C3 convertase and propagating downstream immune responses such as opsonization and inflammation. Pathological overactivation or deficiency of the C1 complex is implicated in diseases like cold agglutinin disease, hereditary angioedema, and systemic lupus erythematosus (PubMed, PMID: 31515370). Modern therapeutic interventions, such as the monoclonal antibody sutimlimab, aim to selectively inhibit C1s activity to treat complement-mediated autoimmune conditions (FDA, Enjaymo Prescribing Information).

Other names

C1 macromolecular complexC1qr2s2Complement component 1C1 esterase

Inhibition of the serine protease activity of the C1s subunit to prevent the cleavage of complement components C4 and C2, thereby halting the classical complement cascade (FDA, Enjaymo Prescribing Information; StatPearls, HAE).