Evidence for Localization of Polymerization Sites in Fibrinogen

Abstract

Abstract It was previously reported (Kudryk, B., Reuterby, J., and Blomback, B. (1973) Thromb. Res. 2, 297) that conjugated fibrinogen, after activation with thrombin, has affinity for Fragment D (Fg-D) obtained by digestion of fibrinogen with plasmin. NH2-terminal analysis of the conjugates suggests that fibrinopeptides are released during activation. Conjugates activated with Reptilase have similar affinity characteristics but show a lower content of glycine NH2-terminal groups, suggesting release of only fibrinopeptide A. Most significant is the finding that a conjugated NH2-terminal CNBr fragment of fibrinogen (N-DSK; (Aα1-51, Bβ1-115, γ1-78)2), after thrombin activation and apparent release of fibrinopeptides, has comparable affinity for Fg-D. All of these different conjugates have the strongest affinity for the high molecular weight subspecies of Fg-D (Fg-Ds). These findings are in favor of the existence of two binding domains in fibrinogen which are important for the fibrinogen-fibrin transition. One domain is in Fg-D and the other is in N-DSK. Experiments with an analog of N-DSK showed that certain structures in N-DSK may be of particular importance for binding or activation, or both.