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The crystal structure of the complex of blood coagulation factor VIIa with soluble tissue factor

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Abstract

Blood coagulation is initiated when tissue factor binds to coagulation factor Vila to give an enzymatically active complex which then activates factors IX and X, leading to thrombin generation and clot formation. We have determined the crystal structure at 2.0-Å resolution of active-site-inhibited factor VIIa complexed with the cleaved extracellular domain of tissue factor. In the complex, factor VIIa adopts an extended conformation. This structure provides a basis for understanding many molecular aspects of the initiation of coagulation.

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References

  1. Kirchhofer, D. et al. Proteins 22, 419–425 (1995).

    Article  CAS  PubMed  Google Scholar 

  2. Nemerson, Y. Blood 71, 1–8 (1988).

    CAS  PubMed  Google Scholar 

  3. Davie, E. W. Thromb. Haemostasis 74, 1–6 (1995).

    CAS  Google Scholar 

  4. Rapaport, S. I. & Rao, L. V. M. Thromb. Haemostasis 74, 7–17 (1995).

    CAS  Google Scholar 

  5. Wilcox, J. N., Smith, K. M., Schwartz, S. M. & Gordon, D. Proc. natn. Acad. Sci. U.S.A. 86, 2839–2843 (1989).

    Article  ADS  CAS  Google Scholar 

  6. Harlos, K. et al. Nature 370, 662–666 (1994).

    Article  ADS  CAS  PubMed  Google Scholar 

  7. Muller, Y. A., Ultsch, M. H., Kelley, R. F. & de Vos, A. M. Biochemistry 33, 10864–10870 (1994).

    Article  CAS  PubMed  Google Scholar 

  8. Ruf, W., Schullek, J. R., Stone, M. J. & Edgington, T. S. Biochemistry 33, 1565–1572 (1994).

    Article  CAS  PubMed  Google Scholar 

  9. Ruf, W. et al. Biochemistry 34, 6310–6315 (1995).

    Article  CAS  PubMed  Google Scholar 

  10. Schullek, J. R., Ruf, W. & Edgington, T. S. J. biol. Chem. 269, 19399–19403 (1994).

    CAS  PubMed  Google Scholar 

  11. Gibbs, C. S., McCurdy, S. N., Leung, L. L. K. & Paborsky, L. R. Biochemistry 33, 14003–14010 (1994).

    Article  CAS  PubMed  Google Scholar 

  12. Kelley, R. F., Costas, K. E., O'Connell, M. P. & Lazarus, R. A. Biochemistry 34, 10383–10392 (1995).

    Article  CAS  PubMed  Google Scholar 

  13. O'Brien, D. P. et al. Biochemistry 33, 14162–14169 (1994).

    Article  CAS  PubMed  Google Scholar 

  14. Martin, D. M. A., Boys, C. W. G. & Ruf, W. FASEB J. 9, 852–859 (1995).

    Article  CAS  PubMed  Google Scholar 

  15. Bode, W., Mayr, I., Baumann, U., Huber, R., Stone, S. R. & Hofsteenge, J. EMBO J. 8, 3467–3475 (1989).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Banner, D. W. & Hadváry, P. J. biol. Chem. 266, 20085–20093 (1991).

    CAS  PubMed  Google Scholar 

  17. Soriano-Garcia, M., Padmanabhan, K., de Vos, A. M. & Tulinsky, A. Biochemistry 31, 2554–2566 (1992).

    Article  CAS  PubMed  Google Scholar 

  18. Graves, B. J. et al. Nature 367, 532–538 (1994).

    Article  ADS  CAS  PubMed  Google Scholar 

  19. Selander-Sunnerhagen, M. et al. J. biol.Chem. 267, 19642–19649 (1992).

    CAS  PubMed  Google Scholar 

  20. Toomey, J. R., Smith, K. J. & Stafford, D. W. J. biol. Chem. 266, 19198–19202 (1991).

    CAS  PubMed  Google Scholar 

  21. Clarke, B. J. et al. FEBS Lett. 298, 206–210 (1992).

    Article  CAS  PubMed  Google Scholar 

  22. Sakai, T., Lund-Hansen, T., Thim, L. & Kisiel, W. J. biol. Chem. 265, 1890–1894 (1990).

    CAS  PubMed  Google Scholar 

  23. Petersen, L. C., Schiødt, J. & Christensen, U. FEBS Lett. 347, 73–79 (1994).

    Article  CAS  PubMed  Google Scholar 

  24. Wildgoose, P., Kazim, A. L. & Kisiel, W. Proc. natn. Acad. Sci. U.S.A. 87, 7290–7294 (1990).

    Article  ADS  CAS  Google Scholar 

  25. Kazama, Y., Pastuszyn, A., Wildgoose, P., Hamamoto, T. & Kisiel, W. J. biol. Chem. 268, 16231–16240 (1993).

    CAS  PubMed  Google Scholar 

  26. Tuddenham, E. G. D., Pemberton, S. & Cooper, D. N. Thromb. Haemostasis 74, 313–321 (1995).

    CAS  Google Scholar 

  27. Waxman, E., Laws, W. R., Laue, T. M., Nemerson, Y. & Ross, J. B. A. Biochemistry 32, 3005–3012 (1993).

    Article  CAS  PubMed  Google Scholar 

  28. Walter, M. R. et al. Nature 376, 230–235 (1995).

    Article  ADS  CAS  PubMed  Google Scholar 

  29. de Vos, A. M., Ultsch, M. & Kossiakoff, A. A. Science 255, 306–312 (1992).

    Article  ADS  CAS  PubMed  Google Scholar 

  30. Thim, L. et al. Biochemistry 27, 7785–7793 (1988).

    Article  CAS  PubMed  Google Scholar 

  31. Freedman, S. J., Furie, B. C., Furie, B. & Baleja, J. D. Biochemistry 34, 12126–12137 (1995).

    Article  CAS  PubMed  Google Scholar 

  32. Sunnerhagen, M. et al. Nature struct. Biol. 2, 504–509 (1995).

    Article  CAS  PubMed  Google Scholar 

  33. Schiødt, J., Harrit, N., Christensen, U. & Petersen, L. C. FEBS Lett. 306, 265–268 (1992).

    Article  PubMed  Google Scholar 

  34. Handford, P. A. et al. EMBO J. 9, 475–480 (1990).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Persson, E. et al. J. biol. Chem. 264, 16897–16904 (1989).

    CAS  PubMed  Google Scholar 

  36. Bjoern, S. et al. J. biol. Chem. 266, 11051–11057 (1991).

    CAS  PubMed  Google Scholar 

  37. Padmanabhan, K. et al. J. molec. Biol. 232, 947–966 (1993).

    Article  CAS  PubMed  Google Scholar 

  38. Banner, D. W. et al. Cell 73, 431–445 (1993).

    Article  CAS  PubMed  Google Scholar 

  39. Sabharwal, A. K. et al. J. biol. Chem. 270, 15523–15530 (1995).

    Article  CAS  PubMed  Google Scholar 

  40. Clackson, T. & Wells, J. A. Science 267, 383–386 (1995).

    Article  ADS  CAS  PubMed  Google Scholar 

  41. Brandstetter, H., Bauer, M., Huber, R., Lollar, P. & Bode, W. Proc. natn. Acad. Sci. U.S.A. 92, 9796–9800 (1995).

    Article  ADS  CAS  Google Scholar 

  42. Husten, E. J., Esmon, C. T. & Johnson, A. E. J. biol. Chem. 262, 12953–12961 (1987).

    CAS  PubMed  Google Scholar 

  43. Mutucumarana, V. P., Duffy, E. J., Lollar, P. & Johnson, A. E. J. biol. Chem. 267, 17012–17021 (1992).

    CAS  PubMed  Google Scholar 

  44. Komiyama, Y., Pedersen, A. H. & Kisiel, W. Biochemistry 29, 9418–9425 (1990).

    Article  CAS  PubMed  Google Scholar 

  45. Otwinowski, Z. in Data Collection and Processing (eds Sawyer, L, Isaacs, N. & Bailey, S.) 56–62 (SERC Daresbury Laboratory, Warrington, 1993).

    Google Scholar 

  46. Navaza, J. Acta crystallogr. A50, 157–163 (1994).

    Article  CAS  Google Scholar 

  47. Collaborative Computational Project, No. 4 Acta crystallogr. D50, 760–763 (1994).

  48. Brünger, A. T. X-PLOR, Version 3.1, A System for X-Ray Crystallography and NMR (Yale Univ. Press, New Haven, CT, 1992).

    Google Scholar 

  49. Kraulis, P. J. J. appl. Crystallogr. 24, 946–950 (1991).

    Article  Google Scholar 

  50. Bacon, D. J. & Anderson, W. F. J. molec. Graph. 6, 219–220 (1988).

    Article  Google Scholar 

  51. Merritt, E. A. & Murphy, M. E. P. Acta crystallogr. D50, 869–873 (1994).

    CAS  Google Scholar 

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Authors and Affiliations

  1. Pharma Division, F. Hoffmann-La Roche, Grenzacherstrasse 124, 4002, Basle, Switzerland

    David W. Banner, Allan D'Arcy, Christiana Chène, Fritz K. Winkler & Daniel Kirchhofer

  2. Department of Medicine, Mount Sinai School of Medicine, New York, New York, 10029, USA

    Arabinda Guha & Yale Nemerson

  3. Department of Biochemistry, Mount Sinai School of Medicine, New York, New York, 10029, USA

    Yale Nemerson

  4. Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticutt, 06510, USA

    William H. Konigsberg

Authors
  1. David W. Banner
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  2. Allan D'Arcy
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  3. Christiana Chène
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  4. Fritz K. Winkler
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  5. Arabinda Guha
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  6. William H. Konigsberg
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  7. Yale Nemerson
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  8. Daniel Kirchhofer
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Banner, D., D'Arcy, A., Chène, C. et al. The crystal structure of the complex of blood coagulation factor VIIa with soluble tissue factor. Nature 380, 41–46 (1996). https://doi.org/10.1038/380041a0

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  • DOI: https://doi.org/10.1038/380041a0

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