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Blood, 1 January 2005, Vol. 105, No. 1, pp. 122-130. Prepublished online as a Blood First Edition Paper on August 12, 2004; DOI 10.1182/blood-2004-06-2176.
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
The
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  S. Harmon, R. J. S. Preston, F. N. Ainle, J. A. Johnson, M. S. Cunningham, O. P. Smith, B. White, and J. S. O'Donnell Dissociation of Activated Protein C Functions by Elimination of Protein S Cofactor Enhancement J. Biol. Chem., November 7, 2008; 283(45): 30531 - 30539. [Abstract] [Full Text] [PDF]
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 B. Saposnik, E. Lesteven, A. Lokajczyk, C. T. Esmon, M. Aiach, and S. Gandrille Alternative mRNA is favored by the A3 haplotype of the EPCR gene PROCR and generates a novel soluble form of EPCR in plasma Blood, April 1, 2008; 111(7): 3442 - 3451. [Abstract] [Full Text] [PDF]
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R. J. S. Preston, E. Ajzner, C. Razzari, S. Karageorgi, S. Dua, B. Dahlback, and D. A. Lane Multifunctional Specificity of the Protein C/Activated Protein C Gla Domain J. Biol. Chem., September 29, 2006; 281(39): 28850 - 28857. [Abstract] [Full Text] [PDF]
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 B. Dahlback and B. O. Villoutreix Regulation of Blood Coagulation by the Protein C Anticoagulant Pathway: Novel Insights Into Structure-Function Relationships and Molecular Recognition Arterioscler Thromb Vasc Biol, July 1, 2005; 25(7): 1311 - 1320. [Abstract] [Full Text] [PDF]
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| Copyright © 2005 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
-carboxyglutamic acid domain of anticoagulant protein S is involved in activated protein C cofactor activity, independently of phospholipid binding
-carboxyglutamic acid (Gla) domain replaced the PS Gla domain in native PS (GlaFII-PS) or in PS deleted of the thrombin-sensitive region (TSR) (GlaFII-
TSR-PS). Neither PS/FII chimera had activated protein C (APC) cofactor activity in plasma clotting assays or purified systems, but both bound efficiently to phospholipids. This pointed to a direct involvement of the PS Gla domain in APC cofactor activity through molecular interaction with APC. Using computational methods, we identified 2 opposite faces of solvent-exposed residues on the PS Gla domain (designated faces 1 and 2) as potentially involved in this interaction. Their importance was supported by functional characterization of a PS mutant in which the face 1 and face 2 PS residues were reintroduced into GlaFII-PS, leading to significant APC cofactor activity, likely through restored interaction with APC. Furthermore, by characterizing PS mutants in which PS face 1 and PS face 2 were individually replaced by the corresponding prothrombin faces, we found that face 1 was necessary for efficient phospholipid binding but that face 2 residues were not strictly required for phospholipid binding and were involved in the interaction with APC.