Protein S binding in relation to the subunit composition of human C4b‐binding protein

Abstract

The human regulatory complement component C4b‐binding protein (C4BP) circulates in plasma either as a free protein or in a bimolecular complex with the vitamin K‐dependent protein S. The major form of C4BP is composed of 7 identical, disulfide‐linked 70 kDa subunits (α‐chains), the arrangement of which gives the C4BP molecule a spider‐like appearance. Recently, we identified a unique 45 kDa subunit (β‐chain) in C4BP. We have now isolated a subpopulation of C4BP, which does notbind protein S. This C4BP species, which had a molecular weight slightly lower than that of the predominant form, was found to lack the β‐chain. Another lower molecular weight form of C4BP was also purified. It contained the β‐chain and was efficient in binding protein S. Its subunit composition was judged to comprise six α‐chains and one β‐chain. These results indicate C4BP in plasma to be heterogeneous at a molecular level vis‐a‐vis subunit composition and/or protein S binding ability and provide support for the concept that the β‐chain of C4BP contains the single protein S binding site.