The tissue factor-factor VII complex: recent advances towards elucidating the structure and function of the initiator...

Localised extravascular initiation of mammalian haemostasis is achieved by the anatomical localization of tissue factor (TF) around blood vessels and at organ surfaces. TF avidly binds factor VII from outflowing blood following vascular injury, forming the tissue factor/factor VII (TF.VII) complex. This is rapidly converted to TF.VIIa, the active initiator of blood coagulation. Structural studies have revealed that the extracellular region of TF consists of two C2-type immunoglobulin-like modules rigidly held at an angle of 125 degrees by an extensive buried interface. The regions of TF involved in binding factor VII extend from the binding finger of the domain interface across quite a wide surface of the distal (N-terminal) module. Solution scattering studies show that both TF and factor VII adopt an extended conformation in solution and that the complex is formed by a compact side by side alignment of the two proteins along their long axes.