Fibrinogen (Fg)

Fibrinogen is an abundant plasma protein (5-10 micrometers) produced in the liver. The intact protein has a molecular weight of 340 kDa and is composed of 3 pairs of disulphide-bound polypeptide chains named A-alpha, B-beta and gamma. Fibrinogen is a triglobular protein consisting of a central E domain and terminal D domains. Proteolysis by thrombin results in release of Fibrinopeptide A (FPA, A-alpha1-16) followed by Fibrinopeptide B (FPB, B-beta 1-14) and the fibrin monomers that result polymerize in a half-overlap fashion to form insoluble fibrin fibrils. The chains of fibrin are referred to as alpha, beta and gamma due to the removal of FPA and FPB. The polymerised fibrin is subsequently stabilized by the transglutaminase activated Factor XIII that forms amide linkages between gamma chains and, to a lesser extent, alpha chains of the fibrin molecules. Proteolysis of fibrinogen by plasmin initially liberates C-terminal residues from the A-alpha chain to produce fragment X (intact D-E-D, which is still clottable). Fragment X is further degraded to non-clottable fragments Y (D-E) and D. Fragment Y can be digested into its constituent D and E fragments. Digestion of non-crosslinked fibrin with plasmin is very similar to the digestion of fibrinogen, which results in production of fragments D and E. Degradation of crosslinked fibrin by plasmin results in fragment DD (D-Dimer consisting of the D domains of 2 fibrin molecules crosslinked via the gamma chains), fragment E (central E domain) as well as DDE in which fragment E is non-covalently associated with DD. For human crosslinked fibrin, the relative weights of the cleavage fragments produced are: 184 kDa for fragment DD, 92 kDa for D, 50 kDa for E, 1.54 kDa for FPA and 1.57 kDa for FPB1-3.