Date of Award

August 2020

Degree Type

Thesis

Degree Name

Master of Science

Department

Biological Sciences

First Advisor

Julie A. Oliver

Committee Members

Heather Owen, Valerica Raicu

Keywords

Forster resonance energy transfer, Oligomerization, Tissue Factor

Abstract

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.

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