Date of Award
Master of Science
Julie A. Oliver
Heather Owen, Valerica Raicu
Forster resonance energy transfer, Oligomerization, Tissue Factor
Tissue Factor (TF) is a transmembrane protein that is the physiologically relevant initiator of blood coagulation. The proteolytic reactions by which the complex of TF with activated coagulation factor VII (TF-FVIIa) activates factor X (FX) to FXa, ultimately leading to production of thrombin and fibrin clot formation has been established. The mechanism by which TF becomes activated from a non-coagulant state remains unclear. One of the competing hypotheses, the TF self-association hypothesis, proposes that oligomerization blocks the docking site for FXa thereby reducing the pro-coagulant activity. Another hypothesis, the allosteric disulfide bond hypothesis, proposes that the redox state causes a conformational change in TF that can affect FXa generation. Resting and stimulated lymphocyte derived cells were analyzed for oligomeric structure. We have shed light on the self-association hypothesis and based on results obtained; conclude that TF self-association may not be responsible for the transformation of TF into a procoagulant form.
Vanderhoof, Brittany S., "Evaluation of One Piece in the Blood Coagulation Puzzle: Exploring an Activation Mechanism of Tissue Factor Through Self-association" (2020). Theses and Dissertations. 2613.
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