C4b-binding protein (C4BP)

C4b-binding protein (C4BP) is a large, multimeric plasma glycoprotein that serves as a primary soluble regulator of the classical and lectin pathways of the complement system (UniProt P04003). It is typically composed of seven alpha-chains and one beta-chain, though other isoforms exist; the alpha-chains contain binding sites for C4b and Factor I, while the beta-chain binds the anticoagulant Protein S, effectively bridging the complement and coagulation systems (Ermert and Blom, 2016). C4BP functions by accelerating the decay of C3-convertases and acting as a cofactor for Factor I-mediated degradation of C4b, thereby preventing runaway complement activation and host tissue damage. In oncology, many tumor cells recruit C4BP to their surface to evade complement-mediated lysis, making the inhibition of C4BP recruitment a potential strategy for enhancing immunotherapy (Olbricht et al., 2021, Frontiers in Immunology). Additionally, various pathogens, such as Neisseria gonorrhoeae and Streptococcus pyogenes, hijack C4BP to survive in human serum, highlighting its role as a target for anti-infective research. Therapeutically, C4BP-based fusion proteins are being explored as anti-inflammatory agents for autoimmune diseases like systemic lupus erythematosus (SLE) to restore complement homeostasis.

Other names

C4BPAC4BPBC4b-binding protein alpha chainC4b-binding protein beta chainProline-rich proteinPRP

C4BP regulates the complement system by acting as a cofactor for the serine protease Factor I in the proteolytic cleavage of C4b and C3b, and by promoting the rapid dissociation (decay acceleration) of the C3-convertase (C4b2a) of the classical and lectin pathways (Blom et al., 2004, Molecular Immunology). It also binds to apoptotic cells and certain pathogens to prevent excessive local inflammation or facilitate immune evasion.