Thermodynamic analysis of the interaction of factor VIII with von Willebrand factor

Biochemistry
J D DimitrovS Lacroix-Desmazes

Abstract

Factor VIII (FVIII) is a glycoprotein that plays an important role in the intrinsic pathway of coagulation. In circulation, FVIII is protected upon binding to von Willebrand factor (VWF), a chaperone molecule that regulates its half-life, distribution, and activity. Despite the biological significance of this interaction, its molecular mechanisms are not fully characterized. We determined the equilibrium and activation thermodynamics of the interaction between FVIII and VWF. The equilibrium affinity determined by surface plasmon resonance was temperature-dependent with a value of 0.8 nM at 35 °C. The FVIII-VWF interaction was characterized by very fast association (8.56 × 10(6) M(-1) s(-1)) and fast dissociation (6.89 × 10(-3) s(-1)) rates. Both the equilibrium association and association rate constants, but not the dissociation rate constant, were dependent on temperature. Binding of FVIII to VWF was characterized by favorable changes in the equilibrium and activation entropy (TΔS° = 89.4 kJ/mol, and -TΔS(++) = -8.9 kJ/mol) and unfavorable changes in the equilibrium and activation enthalpy (ΔH° = 39.1 kJ/mol, and ΔH(++) = 44.1 kJ/mol), yielding a negative change in the equilibrium Gibbs energy. Binding of FVIII to VWF in solid...Continue Reading

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Citations

Dec 17, 2014·Thrombosis Journal·Sven Van PouckeMarcus Lancé
Dec 19, 2012·Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology·Jörg HandschelGünter Giers
Feb 8, 2014·Arteriosclerosis, Thrombosis, and Vascular Biology·Dudley K StricklandSelen C Muratoglu
Jul 1, 2020·Haemophilia : the Official Journal of the World Federation of Hemophilia·Peter L TurecekUNKNOWN iPATH study group
Apr 8, 2020·Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis·Maria BassoRaimondo De Cristofaro
Oct 21, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sofia RossiniJordan D Dimitrov
Apr 2, 2019·The Journal of Physical Chemistry Letters·Antonija KuzmanicFrancesco L Gervasio

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