Visualization of human C4b-binding protein and its complexes with vitamin K-dependent protein S and complement protein C4b.

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Abstract
C4b[complement component 4b]-binding protein (C4bp) participates in the regulation of the C3 convertase of the classical pathway of [human] complement. By binding to C4b, which is one of the structural subunits of this enzyme, C4bp accelerates the decay-dissociation of the enzyme and renders C4b susceptible to degradation by factor I(C3b inactivator). C4bp is a high MW plasma protein (MW = 570,000) composed of apparently identical subunits (MW = 70,000) linked by disulfide bonds. In plasma and in purified form C4bp also forms a bimolecular complex (Kd = 0.9 .times. 10-7 M) with protein S, a recently identified vitamin K-dependent plasma protein. The binding sites on C4bp for protein S and C4b are distinct and noncompetitive and protein S does not influence the function of C4bp as a regulator of the C3 convertase. C4bp, C4b, and protein S were visualized by EM by negative staining. C4bp has an unusual spider-like structure. It is composed of 7 thin (30 A), elongated (330 .ANG.), and flexible subunits that are linked to a small central body. Protein S exhibited 2 globular domains of equal size with a center-to-center distance of .apprxeq. 50 .ANG.. Protein S was bound to the C4bp through only one of its domains by attaching to a short subunit that is distinct from the other 7 subunits. C4b imaged as an irregular, relatively compact molecule. It interacts with the peripheral ends of the elongated subunits, suggesting 7 C4b-binding sites per molecule of C4bp.

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