Human factor VII activation: mechanisms and perspectives Volume 9, issue 2, Mars 2003


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Laboratoire central d‘hématologie, CHU Saint Eloi, Montpellier, France. CRBM‐CNRS‐UPR‐1086 laboratoire de biophysique 1919 route de Mende, Montpellier, France. CEA Valrhô‐site de Marcoule, DSV\DIEP\SBTN, Bagnols‐sur‐Cèze, France.

Activated factor VII (F VIIa) bound to its membrane cofactor tissue factor (TF) triggers the coagulation cascade. TF is essential for the proteolytic activity of FVIIa and is supposed to allosterically regulate F VIIa. The mechanism in which TF completes the zymogen to enzyme transition is still unclear. The recent determination of a F VII zymogen X‐ray structure, when compared to the F T\F VIIa X‐ray structure, reveals an important conformational change in the catalytic domain inside the β‐strand B2, modifying adjacent TF binding regions. Therefore, it is tempting to speculate about the existence of an equilibrium between incompetent and competent TF binding conformations for both F VII and free F VIIa, mediated through the registration in the β‐strand B2. This hypothesis would offer interesting physiological and therapeutic perspectives. However, this mechanism for changing the B2 registrations and its two‐state equilibrium remains to be defined.