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Introduction Hemolysis results in an accumulation of labile heme, which leads to proinflammatory and prothrombotic complications. As a regulatory molecule, heme can affect the function and/or stability of proteins through binding to short, surface-exposed amino acid stretches. As such, the stimulation of the complement and coagulation system through direct heme binding to participating proteins (e.g., C3, fibrinogen, and APC) was described. Method In order to characterize respective heme-bin...Introduction Hemolysis results in an accumulation of labile heme, which leads to proinflammatory and prothrombotic complications. As a regulatory molecule, heme can affect the function and/or stability of proteins through binding to short, surface-exposed amino acid stretches. As such, the stimulation of the complement and coagulation system through direct heme binding to participating proteins (e.g., C3, fibrinogen, and APC) was described. Method In order to characterize respective heme-binding sites in select coagulation proteins in more detail, the potential candidates were screened for potential heme-binding motifs by using the webserver HeMoQuest. Subsequently, these motifs were synthesized as nonapeptides and analyzed for heme binding using UV/vis spectroscopy. Promising sites were further evaluated by molecular docking simulations of the respective heme-protein complexes. Results Heme binding to select procoagulant proteins (e.g., FVIII) is demonstrated by applying a combination of biochemical and spectroscopic approaches. Conclusion The results provided extend our understanding of hemolysis-derived heme as a regulator in the blood coagulation system on the molecular level, which will support the knowledge on the progression of thrombosis under hemolytic conditions. This research is funded by the Society for Thrombosis and Haemostasis Research e.V. (GTH) and the German Research Foundation (DFG).» weiterlesen» einklappen

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