Factor VIIa-tissue factor: functional importance of protein-membrane interactions.
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.
Morrissey
J H
JH
Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City 73104, USA. morrisseyi@omrf.uokhsc.edu
Neuenschwander
P F
PF
Huang
Q
Q
McCallum
C D
CD
Su
B
B
Johnson
A E
AE
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*
D010743:Phospholipids; D013925:Thromboplastin; D015942:Factor VIIa