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Molecular recognition in the protein C anticoagulant pathway.

Dahlbäck, Björn LU and Villoutreix, B O (2003) In Journal of Thrombosis and Haemostasis 1(7). p.1525-1534
Abstract
The protein C (PC) anticoagulant system provides specific and efficient control of blood coagulation. The system comprises circulating or membrane-bound protein components that take part in complicated multimolecular protein complexes being assembled on specific cellular phospholipid membranes. Each of the participating proteins is composed of multiple domains, many of which are known at the level of their three-dimensional structures. The key component of the PC system, the vitamin K-dependent PC, circulates in blood as zymogen to an anticoagulant serine protease. Activation is achieved on the surface of endothelial cells by thrombin bound to the membrane protein thrombomodulin. The endothelial PC receptor binds the Gla domain of PC and... (More)
The protein C (PC) anticoagulant system provides specific and efficient control of blood coagulation. The system comprises circulating or membrane-bound protein components that take part in complicated multimolecular protein complexes being assembled on specific cellular phospholipid membranes. Each of the participating proteins is composed of multiple domains, many of which are known at the level of their three-dimensional structures. The key component of the PC system, the vitamin K-dependent PC, circulates in blood as zymogen to an anticoagulant serine protease. Activation is achieved on the surface of endothelial cells by thrombin bound to the membrane protein thrombomodulin. The endothelial PC receptor binds the Gla domain of PC and stimulates the activation. Activated PC (APC) modulates the activity of blood coagulation by specific proteolytic cleavages of a limited number of peptide bonds in factor (F)VIIIa and FVa, cofactors in the activation of FX and prothrombin, respectively. These reactions occur on the surface of negatively charged phospholipid membranes and are stimulated by the vitamin K-dependent protein S. Regulation of FVIIIa activity by APC is stimulated not only by protein S but also by FV, which, like thrombin, is a Janus-faced protein with both pro- and anticoagulant potential. However, whereas the properties of thrombin are modulated by protein–protein interactions, the specificity of FV function is governed by proteolysis by pro- or anti-coagulant enzymes. The molecular recognition of the PC system is beginning to be unravelled and provides insights into a fascinating and intricate molecular scenario. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Thrombosis and Haemostasis
volume
1
issue
7
pages
1525 - 1534
publisher
Federation of European Neuroscience Societies and Blackwell Publishing Ltd
external identifiers
  • wos:000184170900024
  • pmid:12871288
  • scopus:18244417756
ISSN
1538-7933
DOI
language
English
LU publication?
yes
id
25238d3d-9c71-4cf3-bf2e-e2d4b7c8d7aa (old id 116649)
date added to LUP
2007-07-24 13:26:12
date last changed
2018-05-29 11:00:18
@article{25238d3d-9c71-4cf3-bf2e-e2d4b7c8d7aa,
  abstract     = {The protein C (PC) anticoagulant system provides specific and efficient control of blood coagulation. The system comprises circulating or membrane-bound protein components that take part in complicated multimolecular protein complexes being assembled on specific cellular phospholipid membranes. Each of the participating proteins is composed of multiple domains, many of which are known at the level of their three-dimensional structures. The key component of the PC system, the vitamin K-dependent PC, circulates in blood as zymogen to an anticoagulant serine protease. Activation is achieved on the surface of endothelial cells by thrombin bound to the membrane protein thrombomodulin. The endothelial PC receptor binds the Gla domain of PC and stimulates the activation. Activated PC (APC) modulates the activity of blood coagulation by specific proteolytic cleavages of a limited number of peptide bonds in factor (F)VIIIa and FVa, cofactors in the activation of FX and prothrombin, respectively. These reactions occur on the surface of negatively charged phospholipid membranes and are stimulated by the vitamin K-dependent protein S. Regulation of FVIIIa activity by APC is stimulated not only by protein S but also by FV, which, like thrombin, is a Janus-faced protein with both pro- and anticoagulant potential. However, whereas the properties of thrombin are modulated by protein–protein interactions, the specificity of FV function is governed by proteolysis by pro- or anti-coagulant enzymes. The molecular recognition of the PC system is beginning to be unravelled and provides insights into a fascinating and intricate molecular scenario.},
  author       = {Dahlbäck, Björn and Villoutreix, B O},
  issn         = {1538-7933},
  language     = {eng},
  number       = {7},
  pages        = {1525--1534},
  publisher    = {Federation of European Neuroscience Societies and Blackwell Publishing Ltd},
  series       = {Journal of Thrombosis and Haemostasis},
  title        = {Molecular recognition in the protein C anticoagulant pathway.},
  url          = {http://dx.doi.org/},
  volume       = {1},
  year         = {2003},
}