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• W1890755677 startingPage "e1004346" @default.
• W1890755677 abstract "Fibrinogen is a serum multi-chain protein which, when activated, aggregates to form fibrin, one of the main components of a blood clot. Fibrinolysis controls blood clot dissolution through the action of the enzyme plasmin, which cleaves fibrin at specific locations. Although the main biochemical factors involved in fibrin formation and lysis have been identified, a clear mechanistic picture of how these processes take place is not available yet. This picture would be instrumental, for example, for the design of improved thrombolytic or anti-haemorrhagic strategies, as well as, materials with improved biocompatibility. Here, we present extensive molecular dynamics simulations of fibrinogen which reveal large bending motions centered at a hinge point in the coiled-coil regions of the molecule. This feature, likely conserved across vertebrates according to our analysis, suggests an explanation for the mechanism of exposure to lysis of the plasmin cleavage sites on fibrinogen coiled-coil region. It also explains the conformational variability of fibrinogen observed during its adsorption on inorganic surfaces and it is supposed to play a major role in the determination of the hydrodynamic properties of fibrinogen. In addition the simulations suggest how the dynamics of the D region of fibrinogen may contribute to the allosteric regulation of the blood coagulation cascade through a dynamic coupling between the a- and b-holes, important for fibrin polymerization, and the integrin binding site P1." @default.
• W1890755677 created "2016-06-24" @default.
• W1890755677 creator A5003772180 @default.
• W1890755677 creator A5051903889 @default.
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• W1890755677 date "2015-09-14" @default.
• W1890755677 modified "2023-10-14" @default.
• W1890755677 title "The Internal Dynamics of Fibrinogen and Its Implications for Coagulation and Adsorption" @default.
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• W1890755677 doi "https://doi.org/10.1371/journal.pcbi.1004346" @default.
• W1890755677 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4569070" @default.
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• W1890755677 hasPublicationYear "2015" @default.
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