Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • News & Views
  • Published:

The plot thickens: How thrombin modulates blood clotting

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.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

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.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Michael Overduin.

Rights and permissions

Reprints and permissions

About this article

Cite this article

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

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/74015

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing