Structural biology of factor VIIa/tissue factor initiated coagulation

Front Biosci (Landmark Ed). 2012 Jun 1;17(7):2476-94. doi: 10.2741/4066.


Factor VII (FVII) consists of an N-terminal gamma-carboxyglutamic acid domain followed by two epidermal growth factor-like (EGF1 and EGF2) domains and the C-terminal protease domain. Activation of FVII results in a two-chain FVIIa molecule consisting of a light chain (Gla-EGF1-EGF2 domains) and a heavy chain (protease domain) held together by a single disulfide bond. During coagulation, the complex of tissue factor (TF, a transmembrane glycoprotein) and FVIIa activates factor IX (FIX) and factor X (FX). FVIIa is structurally "zymogen-like" and when bound to TF, it is more "active enzyme-like." FIX and FX share structural homology with FVII. Three structural biology aspects of FVIIa/TF are presented in this review. One, regions in soluble TF (sTF) that interact with FVIIa as well as mapping of Ca2+, Mg2+, Na+ and Zn2+ sites in FVIIa and their functions; two, modeled interactive regions of Gla and EGF1 domains of FXa and FIXa with FVIIa/sTF; and three, incompletely formed oxyanion hole in FVIIa/sTF and its induction by substrate/inhibitor. Finally, an overview of the recognition elements in TF pathway inhibitor is provided.

Publication types

  • Review

MeSH terms

  • Binding Sites
  • Blood Coagulation / physiology*
  • Blood Coagulation Factors / chemistry
  • Blood Coagulation Factors / metabolism
  • Cations / metabolism
  • Factor VIIa / chemistry*
  • Factor VIIa / metabolism*
  • Humans
  • Lipoproteins / chemistry
  • Lipoproteins / metabolism
  • Models, Molecular
  • Multiprotein Complexes / chemistry
  • Protein Folding
  • Protein Interaction Domains and Motifs
  • Thromboplastin / chemistry*
  • Thromboplastin / metabolism*


  • Blood Coagulation Factors
  • Cations
  • Lipoproteins
  • Multiprotein Complexes
  • lipoprotein-associated coagulation inhibitor
  • Thromboplastin
  • Factor VIIa