Structural basis for the anticoagulant activity of the thrombin- thrombomodulin complex

Nature

Volumn 404, Issue 6777, 2000, Pages 518-525

  Fuentes Prior, Pablo ^a   Iwanaga, Yoriko ^a   Huber, Robert ^a   Paglia, Rene ^b   Rumennik, Galina ^b   Seto, Marian ^b   Morser, John ^b   Light, David R ^b   Bode, Wolfram ^a  

^a MAX PLANCK INSTITUTE OF BIOCHEMISTRY   (Germany)

^b BAYER AG   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

ANTICOAGULANT AGENT; THROMBIN ANTITHROMBIN COMPLEX;

AMINO TERMINAL SEQUENCE; ARTICLE; BLOOD CLOTTING; COMPLEX FORMATION; ENZYME ACTIVE SITE; ENZYME SUBSTRATE; FIBRINOLYSIS; MUTAGENESIS; NONHUMAN; PRIORITY JOURNAL; PROTEIN DOMAIN; PROTEIN PROTEIN INTERACTION;

AMINO ACID SEQUENCE; ANTICOAGULANTS; CARBOXYPEPTIDASE U; CARBOXYPEPTIDASES; CRYSTALLOGRAPHY, X-RAY; ELECTROSTATICS; HUMANS; MACROMOLECULAR SUBSTANCES; MODELS, MOLECULAR; MOLECULAR SEQUENCE DATA; PEPTIDE FRAGMENTS; PROTEIN BINDING; PROTEIN C; PROTEIN CONFORMATION; PROTEIN STRUCTURE, TERTIARY; STRUCTURE-ACTIVITY RELATIONSHIP; THROMBIN; THROMBOMODULIN;

EID: 0034732094     PISSN: 00280836     EISSN: None     Source Type: Journal    
DOI: 10.1038/35006683     Document Type: Article

References (37)

1. Davie, E. W., Fujikawa, K. & Kisiel, W. The coagulation cascade: Initiation, maintenance and regulation. Biochemistry 30, 10363-10370 (1991).
2. Esmon, C. T. Thrombomodulin as a model of molecular mechanisms that modulate protease specificity and function at the vessel surface. FASEB J. 9, 946-955 (1995).
3. Bajzat, L., Morser, J. & Nesheim, M. TAFI, or plasma procarboxypeptidase B, couples the coagulation and fibrinolytic cascades through the thrombin-thrombomodulin complex. J. Biol. Chem. 271, 16603-166118 (1996).
4. Gibbs, C. S. et al. Conversion of thrombin into an anticoagulant by protein engineering. Nature 378, 413-416 (1995).
5. Ye, J., Esmon, N. L., Esmon, C. T. & Johnson, A. E. 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. 266, 23016-23021 (1991).
6. Musci, G., Berliner, L. J. & Esmon, C. T. Evidence for multiple conformational changes in the active center of thrombin induced by complex formation with thrombomodulin: an analysis employing nitroxide spin-labels. Biochemistry 27, 769-773 (1988).
7. Vindigni, A., White, C. E., Komives, E. A. & Di Cera, E. Energetics of thrombin-thrombomodulin interaction. Biochemistry 36, 6674-6681 (1997).
8. Di Cera, E., Dang, Q. D. & Ayala, Y. M. Molecular mechanisms of thrombin function. Cell. Mol. Life Sci. 53, 701-730 (1997).
9. Bode, W., Turk, D. & Karshikov, A. The refined 1. 9 Å. X-ray crystal structure of D-Phe-Pro-Arg chloromethylketone-inhibited human alpha-thrombin: Structure analysis, overall structure, electrostatic properties, detailed active-site geometry, and structure-function relationships. Protein Sci. 1, 426-471 (1992).
10. Kurosawa, S., Stearns, D. J., Jackson, K. W. & Esmon, C. T. A 10-kDa cyanogen bromide fragment from the epidermal growth factor homology domain of rabbit thrombomodulin contains the primary thrombin binding site. J. Biol. Chem. 263, 5993-5996 (1988).
11. Mathews, I. I., Padmanabhan, K. P., Tulinksy, A. & Sadler, J. E. Structure of a nonadecapeptide of the fifth EGF domain of thrombomodulin complexed with thrombin. Biochemistry 33, 13547-13552 (1994).
12. Hall, S. W., Nagashima, M., Zhao, L., Morser, J. & Leung, L. L. Thrombin interacts with thrombomodulin, protein C, and thrombin-activatable fibrinolysis inhibitor via specific and distinct domains. J. Biol. Chem. 274, 25510-25516 (1999).
13. Fuentes-Prior, P. et al. Structure of the thrombin complex with triabin, a lipocalin-like exosite-binding inhibitor derived from a triatomine bug. Proc. Natl Acad. Sci. USA 94, 11845-11850 (1997).
14. 2+-mediated binding to protein C. J. Biol. Chem. 266, 19886-19889 (1991).
15. Campbell, I. D. & Bork, P. Epidermal growth factor-like modules. Curr. Opin. Struct. Biol. 3, 385-392 (1993).
16. Downing, A. K. et al. Solution structure of a pair of calcium-binding epidermal growth factor-like domains: implications for the Marfan syndrome and other genetic disorders. Cell 85, 597-605 (1996).
17. Knobe, K. E. et al. Probing the activation of protein C by the thrombin-thrombomodulin complex using structural analysis, site-directed mutagenesis, and computer modeling. Proteins 35, 218-234 (1999).
18. Glaser, C. B. et al. Oxidation of a specific methionine in thrombomodulin by activated neutrophil products blocks cofactor activity. A potential rapid mechanism for modulation of coagulation. J. Clin. Invest. 90, 2565-2573 (1992).
19. Clarke, J. H. et al. The short loop between epidermal growth factor-like domains 4 and 5 is critical for human thrombomodulin function. J. Biol. Chem. 268, 6309-6315 (1993).
20. Nagashima, M., Lundh, E., Leonard, J. C., Morser, J. & Parkinson, J. F. Alanine-scanning mutagenesis of the epidermal growth factor-like domains of human thrombomodulin identifies critical residues for its cofactor activity. J. Biol. Chem. 268, 2888-2892 (1993).
21. 2+. Eur. J. Biochem. 262, 522-533 (1999).
22. Adler, M. et al. The structure of a 19-residue fragment from the C-loop of the fourth epidermal growth factor-like domain of thrombomodulin. J. Biol. Chem. 270, 23366-23372 (1995).
23. Sampoli Benitez, B. A., Hunter, M. J., Meininger, D. P. & Komives, E. A. Structure of the fifth EGF-like domain of thrombomodulin: An EGF-like domain with a novel disulfide-bonding pattern. J. Mol. Biol. 273, 913-926 (1997).
24. Mather, T. et al. The 2.8 Å crystal structure of Gla-domainless activated protein C. EMBO J. 15, 6822-6831 (1996).
25. Hogg, P. J., Ohlin, A. K. & Stenflo, J. Identification of structural domains in protein C involved in its interaction with thrombin-thrombomodulin on the surface of endothelial cells. J. Biol. Chem. 267, 703-706 (1992).
26. Martin, P. D., Malkowski, M. G., Box, J., Esmon, C. T. & Edwards, B. F. New insights into the regulation of the blood clotting cascade derived from the X-ray crystal structure of bovine meizothrombin des F1 in complex with PPACK. Structure 5, 1681-1693 (1997).
27. Gerlitz, B. & Grinnell, B. W. Mutation of protease domain residues Lys37-39 in human protein C inhibits activation by the thrombomodulin-thrombin complex without affecting activation by free thrombin. J. Biol. Chem. 271, 22285-22288 (1996).
28. ** of the protein C serine-protease domain are important for the interaction with the thrombin-thrombomodulin complex. FEBS Lett. 367, 153-157 (1995).
29. Parry, M. A. et al. The ternary microplasmin-staphylokinase-microplasmin complex is a proteinase-cofactor-substrate complex in action. Nature Struct. Biol. 5, 917-923 (1998).
30. Leslie, A. in Crystal. Computing V (eds Moras, D., Podjarny, A. D. & Thierry, J. C.) 27-38 (Oxford Univ. Press, Oxford, 1991).
31. Collaborative Computational Project No. 4. The CCP4 suite: programs for protein crystallography. Acta Crystallogr. D 50, 760-763 (1994).
32. Navaza, J. An automated package for molecular replacement. Acta Crystallogr. A 50, 157-163 (1994).
33. Brünger, G. J. XPLOR (version 3. 1) A System for X-ray Crystallography and NMR (Yale Univ. Press, New Haven, Connecticut, 1993).
34. Meininger, D. P., Hunter, M. J. & Komives, E. A. Synthesis, activity, and preliminary structure of the fourth EGF-like domain of thrombomodulin. Protein Sci. 4, 1683-1695 (1995).
35. Weisel, J. W., Nagaswami, C., Young, T. A. & Light, D. R. The shape of thrombomodulin and interactions with thrombin as determined by electron microscopy. J. Biol. Chem. 271, 31485-31490 (1996).
36. Nicholls, A., Bharadwaj, R. & Honig, B. GRASP- graphical representation and analysis of surface properties. Biophys. J. 64, A166 (1993).
37. Grinnell, B. W., Gerlitz, B. & Berg, D. T. Identification of a region in protein C involved in thrombomodulin-stimulated activation by thrombin: potential repulsion at anion-binding site I in thrombin. Biochem. J. 303, 929-933 (1994).