C4BPB is a component of the C4b-binding protein (C4BP), which is a large glycoprotein composed of seven identical alpha-chains and one unique beta-chain . The beta-chain of C4BP binds to protein S, a vitamin K-dependent protein that serves as a cofactor for activated protein C, which is involved in the regulation of blood coagulation . This interaction highlights the dual role of C4BP in both the complement system and the coagulation system.
The primary function of C4BP is to regulate the classical pathway of complement activation. It acts as a cofactor for the enzyme C3b/C4b inactivator (C3bINA), which hydrolyzes the complement fragment C4b . Additionally, C4BP accelerates the degradation of the C4bC2a complex (C3 convertase) by dissociating the complement fragment C2a . This regulatory role is crucial in preventing the over-activation of the complement system, which can lead to tissue damage and inflammation.
Mutations or dysregulation of the C4BPB gene can be associated with various diseases. For instance, Hemolytic Uremic Syndrome (HUS) and Atypical Hemolytic-Uremic Syndrome (aHUS) are linked to abnormalities in the complement system, including C4BPB . These conditions are characterized by the destruction of red blood cells, kidney failure, and low platelet count.
Moreover, C4BPB has been studied for its potential role as a biomarker. For example, the alpha-chain of C4BP (C4BPα) has been suggested as a biomarker to predict clopidogrel resistance in patients with coronary artery disease . Elevated levels of C4BPα in plasma may indicate a higher sensitivity to clopidogrel, a medication used to prevent blood clots .
Recombinant human C4BPB is produced using recombinant DNA technology, which involves inserting the gene encoding C4BPB into a suitable expression system, such as Escherichia coli (E. coli). The recombinant protein is then purified using conventional chromatography techniques . This recombinant form is used in various research applications to study the function and regulation of the complement system and its role in disease.