The interaction between collagens and factor VIII/von Willebrand factor: investigation of the structural requirements for interaction.
The blood protein Factor VIII/von Willebrand factor (FVIII/VWF) has been shown to bind to a variety of collagen polymers including (i), the native-type fibres (of collagens types I and III), (ii), segment-long-spacing (SLS) aggregates (of collagens types I, III, IV and V), (iii), the insoluble polymer obtained by random cross-linking of the type I monomer and (iv), the non-striated fibril (of type I) produced by alcohol precipitation. Relatively little binding of FVIII/VWF to the amorphous, non-fibrillar form of collagen (type I) produced by salt precipitation from acid solution was observed. No significant binding either to elastin or to the insoluble polymer derived by random cross-linking of bovine serum albumin was noted. The absorption of FVIII/VWF to collagens was affected by ionic concentration and FVIII/VWF was only totally bound at relatively low ionic strength. Binding of radiolabelled FVIII/VWF could be largely inhibited by an excess of the unlabelled protein. The interaction of FVIII/VWF with collagen fibres was inhibited in a concentration-dependent manner by monomeric collagen when present at relatively high concentrations. Gelatin did not appear to inhibit binding significantly. The structural requirements of collagen for binding to occur appear to resemble those required for collagen-induced platelet aggregation in which collagen quaternary structure rather than collagen type per se is the important factor. Loss of secondary or higher orders of structure of FVIII/VWF as a result of heat denaturation or reduction of disulphide bonds decreased or prevented binding. In accord with the association of biological activity with FVIII/VWF aggregates, optimal binding appeared to require the presence of aggregated FVIII/VWF.
D001667:Binding, Competitive; D001779:Blood Coagulation Factors; D055598:Chemical Phenomena; D002621:Chemistry; D003094:Collagen; D005169:Factor VIII; D011485:Protein Binding; D014841:von Willebrand Factor
D001779:Blood Coagulation Factors; D014841:von Willebrand Factor; D005169:Factor VIII; D003094:Collagen