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Title:Blood coagulation reactions on nanoscale membrane surfaces
Author(s):Pureza, Vincent S.
Director of Research:Morrissey, James H.
Doctoral Committee Chair(s):Morrissey, James H.
Doctoral Committee Member(s):Schwartz, Bradford S.; Sligar, Stephen G.; Tajkhorshid, Emad
Department / Program:Biochemistry
Discipline:Biochemistry
Degree Granting Institution:University of Illinois at Urbana-Champaign
Degree:Ph.D.
Genre:Dissertation
Subject(s):blood
coagulation
clotting
tissue factor
prothrombin
prothrombinase
thrombin
tenase
intrinsic
extrinsic
factor VIIa
nanotechnology
Nanodiscs
phospholipids
membranes
anionic
hemostasis
thrombosis
heart disease
hemostatic agent
Abstract:Blood coagulation requires the assembly of several membrane-bound protein complexes composed of regulatory and catalytic subunits. The biomembranes involved in these reactions not only provide a platform for these procoagulant proteins, but can also affect their function. Increased exposure of acidic phospholipids on the outer leaflet of the plasma membrane can dramatically modulate the catalytic efficiencies of such membrane-bound enzymes. Under physiologic conditions, however, these phospholipids spontaneously cluster into a patchwork of membrane microdomains upon which membrane binding proteins may preferentially assemble. As a result, the membrane composition surrounding these proteins is largely unknown. Through the development and use of a nanometer-scale bilayer system that provides rigorous control of the phospholipid membrane environment, I investigated the role of phosphatidylserine, an acidic phospholipid, in the direct vicinity (within nanometers) of two critical membrane-bound procoagulant protein complexes and their respective natural substrates. Here, I present how the assembly and function of the tissue factor·factor VIIa and factor Va·factor Xa complexes, the first and final cofactor·enzyme complexes of the blood clotting cascade, respectively, are mediated by changes in their immediate phospholipid environments.
Issue Date:2010-01-06
URI:http://hdl.handle.net/2142/14739
Rights Information:Copyright 2009 Vincent S. Pureza
Date Available in IDEALS:2010-01-06
2012-01-07
Date Deposited:December 2


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