The interaction of activated factor VII with tissue factor: insight into the mechanism of cofactor-mediated activation of activated factor VII.

The structure solution of the complex of tissue factor (TF) and activated factor VII (FVIIa) and extensive mutagenesis analysis of the FVIIa protease domain have recently provided a detailed, novel insight into the function of the extrinsic activation complex. This overview relates the functional data to the known molecular interactions defined by crystallography, arriving at a hypothesis of how FVIIa is 'switched on' through specific contacts with TF. Combining these findings with the results of mutational analysis of TF, a picture emerges whereby multiple domains of both cofactor and enzyme provide contacts for the assembly of macromolecular substrate.