Calcium-binding sites of the thrombin-thrombomodulin-protein C complex: Possible implications for the effect of platelet factor 4 on the activation of vitamin K-dependent coagulation factors

Thrombosis and Haemostasis

Volumn 97, Issue 6, 2007, Pages 899-906

  Yang, Likui ^a   Rezaie, Alireza R ^a  

^a SAINT LOUIS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Calium; Chondroitin sulfate; Platelet factor 4; Protein C; Thrombin; Thrombomodulin

Indexed keywords

4 CARBOXYGLUTAMIC ACID; BLOOD CLOTTING FACTOR; BLOOD CLOTTING FACTOR 10A; CALCIUM ION; CHONDROITIN SULFATE; MUTANT PROTEIN; PROTEIN C; THROMBIN; THROMBOCYTE FACTOR 4; THROMBOMODULIN; VITAMIN K GROUP;

ARTICLE; BINDING AFFINITY; BINDING SITE; CALCIUM BINDING; CATALYSIS; COMPLEX FORMATION; CONCENTRATION RESPONSE; CONTROLLED STUDY; HUMAN; HUMAN CELL; MOLECULAR RECOGNITION; PRIORITY JOURNAL; PROTEIN DOMAIN; PROTEIN FOLDING; PROTEIN PROTEIN INTERACTION;

BINDING SITES; CALCIUM; CATALYTIC DOMAIN; CELL LINE; CHONDROITIN SULFATES; ENZYME ACTIVATION; HUMANS; MULTIPROTEIN COMPLEXES; MUTATION; PLATELET FACTOR 4; PROTEIN C; PROTEIN CONFORMATION; PROTEIN ENGINEERING; PROTEIN FOLDING; THROMBIN; THROMBOMODULIN; THROMBOPLASTIN; TRANSFECTION; VITAMIN K;

EID: 34250641888     PISSN: 03406245     EISSN: None     Source Type: Journal    
DOI: 10.1160/TH06-12-0697     Document Type: Article

References (42)

1. Stenflo J. Structure-function relationships of epidermal growth factor modules in vitamin K dependent clotting factors. Blood 1991; 78: 1637-1651.
2. Esmon CT, Esmon NL. Protein C activation. Sem Thromb Hemost 1984; 10: 122-130.
3. Walker FJ, Fay PJ. Regulation of blood coagulation by the protein C system. FASEB J 1992; 6: 2561-2567.
4. Dahlbäck B. New molecular insights into the genetics of thrombophilia. Resistance to activated protein C caused by Arg506 to Gln mutation in factor V as a pathogenic risk factor for venous thrombosis. Thromb Haemost 1995; 74: 139-148.
5. Mather T, Oganessyan V. Hof P, et al. The 2.8 Å crystal structure of Gla-domainless activated protein C. EMBO J 1996; 15: 6822-6831.
6. Esmon CT. Molecular events that control the protein C anticoagulant pathway. Thromb Haemost 1993; 70: 1-5.
7. Xu H, Bush LA, Pineda AO, et al. Thrombomodulin changes the molecular surface of interaction and the rate of complex formation between thrombin and protein C. J Biol Chem 2005; 280: 7956-7961.
8. Bode W, Mayr I, Baumann U, et al. The refined 1.9 Å crystal structure of human α-thrombin: interaction with D-Phe-Pro-Arg chlorometheylketone and significance of the Tyr-Pro-Pro-Trp insertion segment. EMBO J 1989; 8: 3467-3475.
9. Rezaie AR, Esmon NL, Esmon CT. The high affinity calcium-binding site involved in protein C activation is outside the first epidermal growth factor homology domain. J Biol Chem 1992; 267: 11701-11704.
10. 2+ for rapid activation by the thrombin-thrombomodulin complex. J Biol Chem 1994; 269: 3151-3154.
11. Bode W, Schwager P. The refined crystal structure of bovine beta-trypsin at 1.8 Å resolution. II. Crystallographic refinement, calcium binding site, benzamidine binding site and active site at pH 7.0. J Mol Biol 1975; 98: 693-717.
12. 2+ binding and biological activity. J Biol Chem 1988; 263: 19240-19248.
13. Rezaie AR, Esmon CT. The function of calcium in protein C activation by thrombin and the thrombin-thrombomodulin complex can be distinguished by mutational analysis of protein C derivatives. J Biol Chem 1992; 267: 26104-26109.
14. Fukudome K, Esmon CT. Identification, cloning and regulation of a novel endothelial cell protein C/activated protein C receptor. J Biol Chem 1994; 269: 26486-26491.
15. Oganesyan V, Oganesyan N, Terzyan S, et al. The crystal structure of the endothelial protein C receptor and a bound phospholipid. J Biol Chem 2002; 277: 24851-24854.
16. Fuentes-Prior P, Iwanaga Y, Huber R, et al. Structural basis for the anticoagulant activity of the thrombin-thrombomodulin complex. Nature 2000; 404: 518-525.
17. Grutter MG, Priestle JP, Rahuel J, et al. Crystal structure of the thrombin-hirudin complex: a novel mode of serine protease inhibition. EMBO J 1990; 9: 2361-2365.
18. Ye J, Esmon NL, Esmon CT, et al. The active site of thrombin is altered upon binding to thrombomodulin: Two distinct structural changes are detected by fluorescence, but only one correlates with protein C activation. J Biol Chem 1991; 266: 23016-23021.
19. Zushi M, Gomi K, Yamamoto S, et al. The last three consecutive epidermal growth factor-like structures of human thrombomodulin comprise the minimum functional domain for protein C-activating cofactor activity and anticoagulant activity. J Biol Chem 1989; 264: 10351-10353.
20. Stearns DJ, Kurosawa S, Esmon CT. Micro-thrombomodulin: Residues 310-486 from the epidermal growth factor precursor homology domain of thrombomodulin will accelerate protein C activation. J Biol Chem 1989; 264: 3352-3356.
21. Meininger DP, Hunter MJ, Komives EA. Synthesis, activity, and preliminary structure of the fourth EGF-like domain of thrombomodulin. Protein Sci 1995; 4: 1683-1695.
22. Yang L, Rezaie AR. The fourth epidermal growth factor-like domain of thrombomodulin interacts with the basic exosite of protein C. J Biol Chem 2003; 278: 10484-10490.
23. Knobe K, Berntsdotter A, Shen L, et al. Probing the activation of protein C by the thrombin-thrombomodulin complex using structural analysis, site-directed mutagenesis, and computer modeling. Proteins 1999; 35: 218-234.
24. Gale AJ, Griffin JH. Characterization of a thrombomodulin binding site on protein C and its comparison to an activated protein C binding site of factor Va. Proteins 2004; 54: 433-441.
25. 2+ dependence of protein C activation. J Biol Chem 1994; 269: 11807-11812.
26. Bourin MC, Lindahl U. Glycosaminoglycans and the regulation of blood coagulation. Biochem J 1993; 289: 313-330.
27. Church FC, Pratt CW, Noyes CM, et al. Structural and functional properties of human alpha-thrombin, phosphopyridoxylated alpha-thrombin, and gammaΓ thrombin. J Biol Chem 1989; 264: 18419-18425.
28. He X, Ye J, Esmon CT, et al. Influence of arginine 93, 97, and 101 of thrombin to its functional specificity. Biochemistry 1997; 36: 8969-8976.
29. Parkinson JF, Grinnell BW, Moore RE, et al. Stable expression of a secretable deletion mutant of recombinant human thrombomodulin in mammalian cells. J Biol Chem 1990; 265: 12602-12610.
30. Slungaard A, Key NS. Platelet factor 4 stimulates thrombomodulin protein C-activating cofactor activity. A structure-function analysis. J Biol Chem 1994; 269: 25549-25556.
31. Amphlett GW, Kisiel W, Castellino FJ. Interaction of calcium with bovine plasma protein C. Biochemistry 1981; 20: 2156-2161.
32. 2+. Eur J Biochem 1999; 262: 522-533.
33. Yang L, Manithody C, Rezaie AR. Activation of protein C by the thrombin-thrombomodulin complex: Cooperative roles of Arg-35 of thrombin and Arg-67 of protein C. Proc Natl Acad Sci USA 2006; 103: 879-884.
34. Smirnov MD, Safa O, Regan LM, et al. A chimeric protein C containing the prothrombin Gla domain exhibits increased anticoagulant activity and altered phospholipid specificity. J Biol Chem 1998; 273: 9031-9040.
35. Rezaie AR. Reactivities of the S2 and S3 subsite residues of thrombin with the native and heparin-induced conformers of antithrombin. Protein Sci 1998; 7: 349-357.
36. Rezaie AR, Yang L. Deletion of the 60-loop provides new insights into the substrate and inhibitor specificity of thrombin. Thromb Haemost 2005; 93: 1047-1054.
37. Smirnov MD, Esmon CT. Phosphatidylethanolamine incorporation into vesicles selectively enhances factor Va inactivation by activated protein C. J Biol Chem 1994; 269: 816-819.
38. Sheehan JP, Sadler JE. Molecular mapping of the heparin-binding exosite of thrombin. Proc Natl Acad Sci USA 1994; 91: 5518-5522.
39. Gan Z-R, Li Y, Chen Z, et al. Identification of basic amino acid residues in thrombin essential for heparin-catalyzed inactivation by antithrombin III. J Biol Chem 1994; 269: 1301-1305.
40. Tsiang M, Jain AK, Gibbs CS. Functional requirement for inhibition of thrombin by antithrombin III in the presence and absence of heparin. J Biol Chem 1997, 272: 12024-12029.
41. Slungaard A. Platelet factor 4 modulation of the thrombomodulin-protein C system. Crit Care Med 2004; 32: S331-335.
42. Eslin DE, Zhang C, Samuels KJ, et al. Transgenic mice studies demonstrate a role for platelet factor 4 in thrombosis: dissociation between anticoagulant and antithrombotic effect of heparin. Blood 2004; 104: 3173-3180.