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

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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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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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  2. Peder Madsen
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  3. Morten K Grøftehauge
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  4. Poul Nissen
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  5. Claus M Petersen
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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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  • DOI: https://doi.org/10.1038/nsmb.1543

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