Biophysical Mechanisms Mediating Fibrin Fiber Lysis

Figure 1

The fibrin molecule and polymerization into fibers. (a) Crystallography-based fibrin molecule: the fibrin molecule structure shown was created using crystal structure 3GHG [9], combined with discrete molecular dynamics methods to fill in amino acids α17–26, α201–610, and β15–57 [15], which were missing in the crystal structure. The α chain is shown in green, β chain in red, and γ chain in blue; disulfide bonds are emphasized as yellow spheres. The αC region was built from homology modeling and molecular dynamics methods as described in [15]. Fibrin degradation fragments D and E are highlighted. Fragment X is formed from plasmin cleavage of the αC region. (b) Cartoon fibrin molecule: upon thrombin cleavage of FpA and FpB, knob A and knob B are exposed to bind the respective hole a and hole b. Cartoon model highlights these interactions and draws structural correlations between the crystal structure and the cartoon (c) Polymerization model for a protofibril: during polymerization, a half-staggered protofibril is formed as the knobs in the central region of one molecule bind to the holes in the distal region of two opposite molecules. Knob B has been implicated in the lateral aggregation of protofibrils and could potentially bind to holes in adjacent protofibrils (not shown).