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Plasminogen is the inactive precursor of the trypsin-like serine protease plasmin. It is normally found circulating through the blood stream. When plasminogen becomes activated and is converted to plasmin, it unfolds a potent enzymatic domain that dissolves the fibrinogen fibers that entgangle the blood cells in a blood clot. This is called fibrinolysis.OVERVIEW OF FUNCTION |
| Fig. 1. BLOOD CLOT. Notice the Fibrin entangling and trapping the red blood cells. (Ref. 1) |
| Fig. 2. Plasminogen binds to PBM. tPa binds to plasminogen and converts it to plasmin. Once converted, plasmin can no longer be bound to PBM and is released to begin cleaving fibrin. (Ref. 5) |
| When a fibrin blood clot is present in the bloodstream, Plasminogen is attracted to the clot. The clot acts almost as a place to sequester the plasminogen long enough for its activator, most commonly tPA, to convert plasminogen into plasmin. Whe plasminogen is activated, it unfolds to expose its potent enzymatic domains. In the above picture, the plasminogen is being sequestered by Plasminogen Binding Material, or PBM (Ref.5). PBM was developed during research to find another material that plasminogen could bind to in order to activate plasmin in significant amounts. PBM serves as an alternative activation source. PBM is generally used in such implants as vascular implants, where fibrin buildup could become a problem. It is put on these implants as a coating, and is used on surfaces of metals, polymers, valve coatings, stents and catheters (Ref. 7) |
| Fig. 3. When plasminogen is activated in a blood clot, it unfolds to expose an enzymatic domain that cleaves fibrinogen fibers. (Ref. 1) |
The activated or open form of plasminogen, plasmin, exposes its many kringles. The kringles are responsible for facilitating protein-protein interactions between plasmin and fibrin. Kringles 1,2,4 and 5 have been shown to display such interactions. Plasmin attacks fibrin at at least 50 different sites. When this occurs, plasmin cleaves the fibers into many fragments, reducing the size of the fibers until they can no longer retain their function of entangling blood cells (Ref. 4). Among these fragments are fragments called D-dimers. A D-dimer is a protein that represents an area of fibrin which contain cross-linked regions used as clot stabilizers. D-dimer present in circulation is used as an indicator of a blood clot being formed and broken down somewhere in the body (Ref. 8,9).Fibrinolysis |
| Fig. 4,5. A representation of the D-dimer cross-linked regions of fibrin before plasmin cleavage. (Ref. 9) |
| Fig. 6. A representation of the variety of crosslinked fibrin breakdown products released into the bloodstream during fibrinolysis. (Ref. 9) |
Plasminogen has also been shown to be used by the Influenza A/WSN/33 (WSN) virus. These viruses possess two envelope glycoproteins, hemagglutinin (HA) and neuraminidase (NA). The cleavage of HA is essential to the infectivity of influenza viruses. The NA of human influenza WSN is able to bind to plasminogen, which is then converted to plasmin. The plasmin is then used to cleave the HA and the virus is able to infect other cells. (Ref. 3)Other Functions of Plasminogen |
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