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oai:www.ideals.illinois.edu:2142/44458 2023-07-11 col_2142_14795 col_2142_5131 com_2142_14794 com_2142_14793 com_2142_8903 com_2142_5130

Morrissey, James H. Morrissey, James H. Gennis, Robert B. Tajkhorshid, Emad Chen, Lin-Feng Ke, Ke 2013-05-24T22:16:48Z 2013-05-24T22:16:48Z 2015-05-24T10:01:24Z 2013-05 2013-05-24T22:16:48Z 2013-05 Initiation of the coagulation cascade in vivo is mediated by tissue factor (TF), which functions as the cell surface receptor and catalytic cofactor for factor VIIa (FVIIa), as well as the mediator for the autoactivation of factor VII (FVII) to FVIIa. Upon vascular injury, TF is exposed to the bloodstream where it comes into contact with FVII(a). The TF/FVIIa complex can be considered as a two-subunit enzyme: TF is the regulatory subunit; and FVIIa is the catalytic subunit. FVIIa does have some proteolytic activity by itself; however, association with TF inserted in an appropriate phospholipid bilayer increases its proteolytic activity on macromolecular substrates many million-fold. The mechanisms by which TF enhances the activity of FVIIa, and the role of the membrane surface in enhancing catalysis by the TF/FVIIa complex are yet not fully understood. To elucidate the mechanisms of the cell-surface complex of TF/FVIIa to trigger the initiation phase of the blood clotting, I investigated how amino acid side chain of TF interacted with anionic phospholipids on cell membranes, and how the TF/FVIIa complex recognized its protein substrates in the context of the membrane. It has been reported that, in vitro, zymogen FVII can be activated to FVIIa via limited proteolysis at a single peptide bond by many proteases, including factor Xa, factor IXa, thrombin, and factor XIIa, as well as FVIIa in complex with TF. By using a FVII mutant (S344A), in which the active site serine residue has been mutated to alanine, an ongoing project is designed to shed light on several unresolved questions regarding FVII activation: 1) which protease plays major role in activating FVII during clotting?; 2) what are the influences of various protein cofactors on FVII activation?; and 3) where and how are the basal levels of the circulating FVIIa generated? Item withdrawn by Mark Zulauf (zulauf@illinois.edu) on 2013-04-12T19:44:31Z Item was in collections: University of Illinois Theses & Dissertations (ID: 1) No. of bitstreams: 1 Ke_Ke.pdf: 2887251 bytes, checksum: 9fff59bf1e9ab7bde609289311c3ec11 (MD5) Made available in DSpace on 2013-05-24T22:16:48Z (GMT). No. of bitstreams: 2 Ke_Ke.pdf: 2887439 bytes, checksum: de656ea28581328b2b12f39126f8edc7 (MD5) license.txt: 4052 bytes, checksum: c3aa0354033bdc6a577352fac0da83a7 (MD5) Restriction data tranferred 2014-07-01T11:36:14-05:00 Original Data Group with Access UIUC Users [automated] Release Date: 2015-05-24 17:18:31 UTC Reason: Author requested U of Illinois access only (OA after 2yrs) in Vireo ETD system Item marked as restricted to the 'UIUC Users [automated]' Group (id=2) by Seth Robbins (srobbins@illinois.edu) on 2013-05-24T22:19:08Z Item is restricted until 2015-05-24T22:18:31Z U of I Only Restriction Lifted for Item 44431 on 2015-05-24T10:01:24Z. http://hdl.handle.net/2142/44458 en Copyright 2013 Ke Ke blood coagulation coagulation factors tissue factor factor VIIa factor X membranes The tissue factor-factor VII(a) complex in blood coagulation text Biochemistry 1438 Biochemistry 0318 University of Illinois at Urbana-Champaign Dissertation Ph.D. PHD:Biochemistry -UIUC 10KS0318PHD