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Dissecting Functional Interactions in Coagulation Protein Complexes by Use of NMR Spectroscopy

[ Vol. 3 , Issue. 3 ]


Dmitri Talkatchev, Anatol Koutychenko and Feng Ni   Pages 275 - 285 ( 11 )


The blood coagulation cascade can be considered as a system of well-orchestrated protein activation reactions involving and leading to the formation of large macromolecular assemblies. NMR investigations performed during the last six years have focused on the structural, motional and binding properties of some protein domains and interfaces critical for the formation of these protein complexes, outlining sophisticated intermolecular adaptations. The studied protein domains are either single molecules or covalently-linked heterodimers of the epidermal growth factor (EGF) homology domains, calcium-binding EGF domains and γ-carboxyglutamic(Gla)-containing domains responsible for calcium-dependent binding to cell membranes. The characterized binding interfaces have included those between thrombin and fibrinogen, between thrombin and thrombomodulin, between factor VIIIa and the cell membrane, between tissue factor and factor VIIa, and most recently between factor Va and prothrombin. The obtained results indicate that the regulation of blood coagulation by protein and low molecular weight cofactors may involve a significant degree of protein folding transitions with changes in molecular and conformational motions coupled to enzymatic activities. This new level of complexity of the molecular processes controlling coagulation may lead to novel strategies for the development of more effective therapeutic anticoagulants.


coagulation protein complex, tf-fviia complex, fvii-egf1 domain, gla-egf, egf1


Biomolecular NMR Laboratory and the Montreal Joint Centre for Structural Biology, Biotechnology Research Institute, National Research Council of Canada, 6100 Royalmount Avenue, Montreal, Quebec, Canada H4P 2R2

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