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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References
Petersen, C.M. et al. J. Biol. Chem. 272, 3599–3605 (1997).
Jacobsen, L. et al. J. Biol. Chem. 271, 31379–31383 (1996).
Hampe, W., Rezgaoui, M., Hermans-Borgmeyer, I. & Schaller, H.C. Hum. Genet. 108, 529–536 (2001).
Mazella, J. et al. J. Biol. Chem. 273, 26273–26276 (1998).
Munck Petersen, C. et al. EMBO J. 18, 595–604 (1999).
Nykjaer, A. et al. Nature 427, 843–848 (2004).
Teng, H.K. et al. J. Neurosci. 25, 5455–5463 (2005).
Westergaard, U.B. et al. J. Biol. Chem. 279, 50221–50229 (2004).
Maeda, S. et al. J. Cell. Physiol. 193, 73–79 (2002).
Nielsen, M.S., Jacobsen, C., Olivecrona, G., Gliemann, J. & Petersen, C.M. J. Biol. Chem. 274, 8832–8836 (1999).
Nielsen, M.S. et al. EMBO J. 20, 2180–2190 (2001).
Nakamura, K., Namekata, K., Harada, C. & Harada, T. Cell Death Differ. 14, 1552–1554 (2007).
Jansen, P. et al. Nat. Neurosci. 10, 1449–1457 (2007).
Nilsson, S.K. et al. J. Biol. Chem. 283, 25920–25927 (2008).
Vincent, J.P., Mazella, J. & Kitabgi, P. Trends Pharmacol. Sci. 20, 302–309 (1999).
Garlow, S.J., Boone, E., Kinkead, B. & Nemeroff, C.B. Neuropsychopharmacology 31, 535–543 (2006).
Mazella, J. & Vincent, J.P. Peptides 27, 2469–2475 (2006).
Martin, S., Navarro, V., Vincent, J.P. & Mazella, J. Gastroenterology 123, 1135–1143 (2002).
He, X.L. & Garcia, K.C. Science 304, 870–875 (2004).
Zsurger, N., Mazella, J. & Vincent, J.P. Brain Res. 639, 245–252 (1994).
Rasmussen, H.B., Branner, S., Wiberg, F.C. & Wagtmann, N. Nat. Struct. Biol. 10, 19–25 (2003).
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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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.
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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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