Complement component 4-binding protein (C4BP) is a plasma glycoprotein that inhibits the classical pathway of complement activation, which is mediated through antibody targeting of foreign antigen. Structurally, C4BP is a disulfide linked, multimeric protein that is composed of seven alpha chains and one beta chain. C4BP functions as a cofactor for C3beta inactivator in the cleavage of C3beta, and accelerates the decay of C4betaC2alpha (C3 convertase) by acting as a cofactor in the cleavage of C4beta by factor I. Streptococcal strains that express Ig-binding cell surface molecules, which are members of the M protein family, can bind to overlapping C4beta binding sites in C4BP and therefore, interfere with the classical pathway of complement activation. Bacteria-bound C4BP may be an evolved mechanism that downregulates complement activation in the bacterial host microenvironment, thereby reducing the occurrences of bacterial opsonization and phagocytosis.
C4b-binding protein beta chain