title: Factor VIIa-tissue factor: functional importance of protein-membrane interactions.
abstract: The first enzyme in the blood clotting cascade consists of two distinct protein subunits: a catalytic subunit (factor VIIa; FVIIa) and an essential regulatory subunit (tissue factor; TF). FVIIa is a soluble plasma protease, while TF is a cell-surface, integral-membrane protein. The recently reported X-ray crystal structure of the complex of FVIIa and the isolated extracellular domain of TF has provided important insights into the protein-protein interactions that bind these two subunits together (1). Equally important in the functioning of the TF-FVIIa complex, but much less well understood, are a series of protein-phospholipid interactions involving TF, FVIIa, and the natural substrates of this enzyme, as well as protein-protein interactions important in substrate recognition by TF-FVIIa. Here we review recent studies on the membrane organization and role of protein-phospholipid interactions in the function of TF-FVIIa, the enzyme that triggers blood clotting in hemostasis and thrombosis.
authors.affiliation: Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City 73104, USA. morrisseyi@omrf.uokhsc.edu
authors.forename: J H
authors.initials: JH
authors.lastname: Morrissey
authors.forename: P F
authors.initials: PF
authors.lastname: Neuenschwander
authors.forename: Q
authors.initials: Q
authors.lastname: Huang
authors.forename: C D
authors.initials: CD
authors.lastname: McCallum
authors.forename: B
authors.initials: B
authors.lastname: Su
authors.forename: A E
authors.initials: AE
authors.lastname: Johnson
mesh_terms: D018360:Crystallography, X-Ray; D015942:Factor VIIa / Q000502:physiology*; D006801:Humans; D008566:Membranes / Q000502:physiology; D010743:Phospholipids / Q000502:physiology; D017434:Protein Structure, Tertiary; D013925:Thromboplastin / Q000502:physiology*
chemical_list: D010743:Phospholipids; D013925:Thromboplastin; D015942:Factor VIIa