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.

  • Brief Communication
  • Published:

Crystal structures of two human vitronectin, urokinase and urokinase receptor complexes

Nature Structural & Molecular Biology volume 15, pages 422–423 (2008)Cite this article

Abstract

The urokinase receptor (uPAR) can recognize several ligands. The structural basis for this multiple ligand recognition by uPAR is unknown. This study reports the crystal structures of uPAR in complex with both urokinase (uPA) and vitronectin and reveal that uPA occupies the central cavity of the receptor, whereas vitronectin binds at the outer side of the receptor. These results provide a structural understanding of one receptor binding to two ligands.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

Figure 1: Recognition of both the uPA N-terminal fragment (ATF) and the vitronectin SMB domain by uPAR.
Figure 2: Details of the uPAR–SMB interface.

Similar content being viewed by others

Accession codes

Primary accessions

Protein Data Bank

References

  1. Blasi, F. & Carmeliet, P. Nat. Rev. Mol. Cell Biol. 3, 932–943 (2002).

    Article  CAS  Google Scholar 

  2. Llinas, P. et al. EMBO J. 24, 1655–1663 (2005).

    Article  CAS  Google Scholar 

  3. Huai, Q. et al. Science 311, 656–659 (2006).

    Article  CAS  Google Scholar 

  4. Wei, Y. et al. J. Biol. Chem. 269, 32380–32388 (1994).

    CAS  PubMed  Google Scholar 

  5. Deng, G., Royle, G., Wang, S., Crain, K. & Loskutoff, D.J. J. Biol. Chem. 271, 12716–12723 (1996).

    Article  CAS  Google Scholar 

  6. Gardsvoll, H. & Ploug, M. J. Biol. Chem. 282, 13561–13572 (2007).

    Article  CAS  Google Scholar 

  7. Sidenius, N., Andolfo, A., Fesce, R. & Blasi, F. J. Biol. Chem. 277, 27982–27990 (2002).

    Article  CAS  Google Scholar 

  8. Yuan, C. & Huang, M. Cell. Mol. Life Sci. 64, 1033–1037 (2007).

    Article  CAS  Google Scholar 

  9. Madsen, C.D., Ferraris, G.M., Andolfo, A., Cunningham, O. & Sidenius, N. J. Cell Biol. 177, 927–939 (2007).

    Article  CAS  Google Scholar 

  10. Zhou, A., Huntington, J.A., Pannu, N.S., Carrell, R.W. & Read, R.J. Nat. Struct. Biol. 10, 541–544 (2003).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This research is supported by grants from the US National Institutes of Health (HL08658) and the American Heart Association (0330089N) (to M.H.) and from the British Heart Foundation (to A.Z.). Data for this study were measured at beam lines ID19 and ID24 of Advanced Photon Sources and at beam line X29 of the the National Synchrotron Light Source.

Author information

Authors and Affiliations

  1. Division of Hemostasis and Thrombosis, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, 02215, Massachusetts, USA

    Qing Huai, Lin Lin, Bruce Furie, Barbara C Furie & Mingdong Huang

  2. Department of Haematology, University of Cambridge, Cambridge Institute for Medical Research, Wellcome Trust/MRC Building, Hills Road, Cambridge, CB2 2XY, UK

    Aiwu Zhou

  3. Attenuon, LLC, 11535 Sorrento Valley Rd, Suite 401, San Diego, 92121, California, USA

    Andrew P Mazar, Graham C Parry & Jennifer Callahan

  4. D.E. Shaw Research and Development, 39th Floor, Tower 45, 120 West Forty-Fifth Street, New York, 10036, New York, USA

    David E Shaw

Authors
  1. Qing Huai
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Aiwu Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lin Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Andrew P Mazar
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Graham C Parry
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jennifer Callahan
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. David E Shaw
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Bruce Furie
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Barbara C Furie
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Mingdong Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Q.H. and L.L. performed the experiments and solved the structures; M.H. refined the structures and wrote the paper; A.Z., A.P.M., G.C.P., J.C., D.E.S., B.F. and B.C.F. provided reagents and/or ideas to this work.

Corresponding author

Correspondence to Mingdong Huang.

Supplementary information

Supplementary Text and Figures

Supplementary Figure 1, Supplementary Tables 1 and 2, and Supplementary Methods (PDF 1265 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Huai, Q., Zhou, A., Lin, L. et al. Crystal structures of two human vitronectin, urokinase and urokinase receptor complexes. Nat Struct Mol Biol 15, 422–423 (2008). https://doi.org/10.1038/nsmb.1404

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nsmb.1404

This article is cited by

Search

Advanced 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