How is plasminogen converted to plasmin?
Plasminogen is activated by endogenous, natural activators, and exogenous activators. Activation by its natural activators, tPA and uPA, involves a bond cleavage at a specific site in the plg molecule, which gives rise to a two-chain molecule linked by two disulfide bonds. tPA binding to fibrin concentrates and correctly orientates the tPA and plasminogen, as well as inducing a conformational changes in the molecules that promote efficient clot lysis. uPA can only activate plasminogen in the presence of fibrin, but it does not bind to, nor is it activated by fibrin. Streptokinase is an exogenous plasminogen activator and functions by forming a 1:1 complex with human plg. This complex can function as an activator of other plg molecules. Complex formation is accompanied by a conformational change in the plg molecule, exposing the active site.