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The plot thickens: How thrombin modulates blood clotting

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The tide of the blood coagulation cascade turns by a switch in thrombin specificity. Two new structures reveal how thrombomodulin's EGF domains flip the switch by blocking old substrates and docking new ones.

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Figure 1: The blood coagulation cascade involves proteolytic activation of a series of membrane bound proteases.
Figure 2: Structure of thrombomodulin's EGF domains in the thrombin-bound and free states.

References

  1. Wood, M.J., Sampoli Benitez, B. A. & Komives, E. A. Nature Struct. Biol. 7, 200–204 (2000).

    Article  CAS  Google Scholar 

  2. Fuentes-Prior, P. et al. Nature in the press (2000).

  3. Ferry, J.D. & Morrison, P.R. J. Am. Chem. Soc. 69, 388–399 (1947).

    Article  CAS  Google Scholar 

  4. Kisiel, W., Ericsson, L.H. & Davie, E.W. Biochemistry 15, 4893–4900 (1976).

    Article  CAS  Google Scholar 

  5. Bajzar, L., Manuel, R. & Nesheim, M. E. J. Biol. Chem. 270, 14477–14484 (1995).

    Article  CAS  Google Scholar 

  6. Esmon, C.T. & Owen, W.G. Proc. Natl. Acad. Sci. USA 78, 2249–2252 (1981).

    Article  CAS  Google Scholar 

  7. Esmon, C.T. FASEB J. 9, 946–955 (1995).

    Article  CAS  Google Scholar 

  8. White C.E. et al. Proc. Natl. Acad. Sci. USA 93, 10177–10182 (1996).

    Article  CAS  Google Scholar 

  9. White, C.E. et al. Protein Eng. 8, 1177–1187 (1995).

    Article  CAS  Google Scholar 

  10. Sampoli Benitez, B.A., Hunter, M. J., Meininger, D. P. & Komives, E.A. J. Mol. Biol. 273, 913–926 (1997).

    Article  CAS  Google Scholar 

  11. Light, D.R. et al. Eur J. Biochem. 262, 522–533 (1999).

    Article  CAS  Google Scholar 

  12. Mathews I.I., Padmanabhan, K.P., Tulinsky, A. & Sadler, J.E. Biochemistry 33, 13547–13552 (1994)

    Article  CAS  Google Scholar 

  13. Mather, T. et al. EMBO J. 15, 6822–6831 (1996).

    Article  CAS  Google Scholar 

  14. Zushi, M. J. Biol. Chem. 266, 19886–19889 (1991).

    CAS  PubMed  Google Scholar 

  15. Knobe, K.E. et al. Proteins 35, 218–234 (1999).

    Article  Google Scholar 

  16. Nesheim, M. et al. Thromb. Haemost. 78, 386–391 (1997).

    Article  CAS  Google Scholar 

  17. Fareed, J. et al. Semin. Hematol. 36, 42–56 (1999).

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank P. Fuentes-Prior and M.J. Wood for providing atomic coordinates, and J. Mamay for helping with figure preparation.

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Authors and Affiliations

  1. the Department of Pharmacology and Biomolecular Structure Program, University of Colorado Health Sciences Center, Denver, 80220, Colorado, USA

    Michael Overduin & Tonny de Beer

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  1. Michael Overduin
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  2. Tonny de Beer
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Correspondence to Michael Overduin.

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Overduin, M., de Beer, T. The plot thickens: How thrombin modulates blood clotting. Nat Struct Mol Biol 7, 267–269 (2000). https://doi.org/10.1038/74015

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