Structural basis for sequential cleavage of fibrinopeptides upon fibrin assembly

Details of the crystal structure of human thrombin in complex with the central part of human fibrin are revealed and results are presented of the molecular modeling of the fibrinopeptides A and B (fpA- and fpB-) containing portions of the Aalpha and Bbeta chains, in both fibrinogen and protofibrils. Analysis provides a coherent rationale for the preferential removal of fpA from fibrinogen at the first stage of fibrin assembly and the accelerated cleavage of fpB from protofibrils at the second stage.