Affinity chromatography of various fibrinogen and fibrin fragments on Lys-plasminogen-Sepharose was used to localize the plasminogen-binding sites in human fibrin(ogen). The fragments studied in the present investigation were derived from the central (E) and the terminal (D) globular domains of fibrinogen and fibrin. Our results showed that these two different, sequentially nonidentical domains of fibrin(ogen) both carry plasminogen-binding sites. Competitive affinity chromatography of fragment D1 and fragments derived from it by proteolytic modification of its D γ-chain revealed that this modification causes an 11-fold increase of the association constant of the interaction with Lys-plasminogen-Sepharose. This suggests that the carboxy-terminal region of the D γ-chain is involved in controlling the plasminogen-binding site of the D domain. In contrast with its fragments, intact fibrinogen is not retained by Lys-plasminogen-Sepharose, indicating that the plasminogen-binding sites present in the constituent E and D domains are not fully functional in the parent molecule. It seems possible that the plasminogen-binding sites are present but hidden in fibrinogen and proteolytic dissection of the molecule uncovers these sites in E and D fragments by removing peptides masking the plasminogen-binding regions.
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