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Ligands bind to Sortilin in the tunnel of a ten-bladed β-propeller domain

Nature Structural & Molecular Biology volume 16, pages 96–98 (2009)Cite this article

Abstract

The structure of the Sortilin ectodomain in complex with neurotensin has been determined at 2-Å resolution, revealing that the C-terminal part of neurotensin binds in the tunnel of a ten-bladed β-propeller domain. Binding competition studies suggest that additional binding sites, for example, for the prodomain of nerve growth factor-β, are present in the tunnel and that competition for binding relates to the restricted space inside the propeller.

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Figure 1: The structure of sSortilin.
Figure 2: Effects of neurotensin and derived peptides on sSortilin binding.

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References

  1. Petersen, C.M. et al. J. Biol. Chem. 272, 3599–3605 (1997).

    Article  CAS  Google Scholar 

  2. Jacobsen, L. et al. J. Biol. Chem. 271, 31379–31383 (1996).

    Article  CAS  Google Scholar 

  3. Hampe, W., Rezgaoui, M., Hermans-Borgmeyer, I. & Schaller, H.C. Hum. Genet. 108, 529–536 (2001).

    Article  CAS  Google Scholar 

  4. Mazella, J. et al. J. Biol. Chem. 273, 26273–26276 (1998).

    Article  CAS  Google Scholar 

  5. Munck Petersen, C. et al. EMBO J. 18, 595–604 (1999).

    Article  CAS  Google Scholar 

  6. Nykjaer, A. et al. Nature 427, 843–848 (2004).

    Article  CAS  Google Scholar 

  7. Teng, H.K. et al. J. Neurosci. 25, 5455–5463 (2005).

    Article  CAS  Google Scholar 

  8. Westergaard, U.B. et al. J. Biol. Chem. 279, 50221–50229 (2004).

    Article  CAS  Google Scholar 

  9. Maeda, S. et al. J. Cell. Physiol. 193, 73–79 (2002).

    Article  CAS  Google Scholar 

  10. Nielsen, M.S., Jacobsen, C., Olivecrona, G., Gliemann, J. & Petersen, C.M. J. Biol. Chem. 274, 8832–8836 (1999).

    Article  CAS  Google Scholar 

  11. Nielsen, M.S. et al. EMBO J. 20, 2180–2190 (2001).

    Article  CAS  Google Scholar 

  12. Nakamura, K., Namekata, K., Harada, C. & Harada, T. Cell Death Differ. 14, 1552–1554 (2007).

    Article  CAS  Google Scholar 

  13. Jansen, P. et al. Nat. Neurosci. 10, 1449–1457 (2007).

    Article  CAS  Google Scholar 

  14. Nilsson, S.K. et al. J. Biol. Chem. 283, 25920–25927 (2008).

    Article  CAS  Google Scholar 

  15. Vincent, J.P., Mazella, J. & Kitabgi, P. Trends Pharmacol. Sci. 20, 302–309 (1999).

    Article  CAS  Google Scholar 

  16. Garlow, S.J., Boone, E., Kinkead, B. & Nemeroff, C.B. Neuropsychopharmacology 31, 535–543 (2006).

    Article  CAS  Google Scholar 

  17. Mazella, J. & Vincent, J.P. Peptides 27, 2469–2475 (2006).

    Article  CAS  Google Scholar 

  18. Martin, S., Navarro, V., Vincent, J.P. & Mazella, J. Gastroenterology 123, 1135–1143 (2002).

    Article  CAS  Google Scholar 

  19. He, X.L. & Garcia, K.C. Science 304, 870–875 (2004).

    Article  CAS  Google Scholar 

  20. Zsurger, N., Mazella, J. & Vincent, J.P. Brain Res. 639, 245–252 (1994).

    Article  CAS  Google Scholar 

  21. Rasmussen, H.B., Branner, S., Wiberg, F.C. & Wagtmann, N. Nat. Struct. Biol. 10, 19–25 (2003).

    Article  CAS  Google Scholar 

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Acknowledgements

We would like to thank the Lundbeck Foundation for financial support. C. Jacobsen and L. Sottrup-Jensen are thanked for assistance with the SPR-analysis and fluorescence measurements. Financial support from DANSYNC and help from staff at the synchrotrons at MAX-Lab (Lund), European Molecular Biology Laboratory outstation at Deutsches Elektronen Synchrotron (EMBL/DESY, Hamburg) and the Swiss Light Source (SLS, Zurich) is also gratefully acknowledged.

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Authors and Affiliations

  1. Department of Molecular Biology, MIND Centre, University of Aarhus, Gustav Wieds Vej 10C, Århus C, DK 8000, Denmark

    Esben M Quistgaard, Morten K Grøftehauge, Poul Nissen & Søren S Thirup

  2. MIND Centre, Institute of Medical Biochemistry, University of Aarhus, Ole Worms Allé 1170, Århus C, DK 8000, Denmark

    Peder Madsen & Claus M Petersen

Authors
  1. Esben M Quistgaard
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  4. Poul Nissen
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  6. Søren S Thirup
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Contributions

E.M.Q. performed the crystallization, structure determination and writing of the paper; P.M. performed protein preparation, binding measurements, mutagenesis and chase experiments; M.K.G. performed fluorescence spectroscopy and contributions to structure determination; P.N. co-supervised the project; C.M.P. and S.S.T. wrote the paper and supervised the project.

Corresponding authors

Correspondence to Claus M Petersen or Søren S Thirup.

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Supplementary Text and Figures

Supplementary Figures 1–5, Supplementary Table 1 and Supplementary Methods. (PDF 6129 kb)

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Quistgaard, E., Madsen, P., Grøftehauge, M. et al. Ligands bind to Sortilin in the tunnel of a ten-bladed β-propeller domain. Nat Struct Mol Biol 16, 96–98 (2009). https://doi.org/10.1038/nsmb.1543

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