High molecular weight complex in human plasma between vitamin K-dependent protein S and complement component C4b-binding protein.

TLDR

C4b‑binding protein regulates complement activation and exists in equilibrium with free protein S in plasma, though the role of protein S in the complex remains unknown. Uncomplexed C4b‑binding protein was isolated from plasma supernatant after barium citrate adsorption. Protein S circulates both freely and bound to C4b‑binding protein, with the majority of C4b‑binding protein forming a noncovalently linked complex that dissociates with NaDodSO4 and serves as a major barium citrate‑adsorbing protein; the two forms have identical subunit masses after reduction.

Abstract

Protein S, a recently described vitamin K-dependent plasma protein, is shown to exist in two forms in plasma--free protein and in complex with C4b-binding protein. C4b-binding protein is involved in the regulation of the rate of complement activation. A major proportion of C4b-binding protein in plasma is in complex with protein S. The complex is a major and previously unrecognized component of the group of plasma proteins that adsorbs to barium citrate. The complex dissociates in the presence of NaDodSO4, indicating that C4b-binding protein and protein S are held together by noncovalent bonds. Uncomplexed C4b-binding protein was purified from the supernatant after barium citrate adsorption. On NaDodSO4/polyacrylamide gels without reduction, it appeared to have a slightly faster migration rate than the C4b-binding protein dissociated from the complex with protein S. After reduction, the subunits of the two forms of C4b-binding protein appeared to have identical molecular weights. Furthermore, there is an equilibrium between free and bound protein S in plasma. The role of protein S in the complex is unknown.