Plasminogen-fibrin and plasminogen-urokinase-type plasminogen activator receptor interfaces (PLG-Fibrin and PLG-uPA/uPAR interfaces)

The plasminogen–fibrin and plasminogen–uPA/uPAR interfaces are essential protein-protein interaction sites that regulate the fibrinolytic system and pericellular proteolysis. Plasminogen (PLG) contains five kringle domains with lysine-binding sites (LBS) that mediate its attachment to C-terminal lysines on fibrin or the urokinase-type plasminogen activator receptor (uPAR) complex (UniProt: P00747). The PLG-fibrin interface localizes plasmin generation to blood clots, where fibrin acts as a cofactor for tissue-type plasminogen activator (tPA), ensuring efficient thrombus dissolution (PubMed: 22507812). The PLG-uPA/uPAR interface facilitates localized proteolysis on cell surfaces, a process critical for cell migration, tissue remodeling, and wound healing (PubMed: 11031251). In oncology, these interfaces are often upregulated to promote tumor invasion and metastasis. Therapeutic agents like tranexamic acid and aminocaproic acid act as lysine analogs that competitively block these interfaces to inhibit fibrinolysis and manage bleeding (StatPearls: NBK532909). Conversely, plasminogen activators like alteplase target these interfaces to treat acute ischemic events by promoting plasmin-mediated fibrin degradation.

Other names

Plasminogen lysine-binding sitesPLG-Fibrin interfacePLG-uPA/uPAR complexFibrinolytic assemblyPlasminogen-binding sites

Competitive inhibition of plasminogen binding to fibrin or cell-surface receptors via lysine-binding sites; enzymatic activation of plasminogen to plasmin.