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PMID: 19122660 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

Nature structural & molecular biology ·Vol. 16 ·No. 1 ·2009-01-00 ·Pages 96-8

Quistgaard EM, Madsen P, Grøftehauge MK, Nissen P, Petersen CM, Thirup SS

Abstract

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

MeSH Terms
Adaptor Proteins, Vesicular Transport/chemistry,metabolism Animals Apoptosis Binding Sites Ligands Mammals Models, Molecular Neurons/physiology Neurotensin/chemistry,metabolism Protein Binding Protein Conformation
Chemicals
Adaptor Proteins, Vesicular Transport Ligands Neurotensin sortilin
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Quistgaard Esben M
MIND Centre, Department of Molecular Biology, University of Aarhus, Gustav Wieds Vej 10C, DK 8000 Arhus C, Denmark.
Madsen Peder
Grøftehauge Morten K
Nissen Poul
Petersen Claus M
Thirup Søren S
References (21)
21 references, click to expand
  1. Sortilin is upregulated during osteoblastic differentiation of mesenchymal stem cells and promotes extracellular matrix mineralization.
    J Cell Physiol. 2002 Oct;193(1):73-9 PMID: 12209882
  2. Neurotensin receptor-1 and -3 complex modulates the cellular signaling of neurotensin in the HT29 cell line.
    Gastroenterology. 2002 Oct;123(4):1135-43 PMID: 12360476
  3. ProBDNF induces neuronal apoptosis via activation of a receptor complex of p75NTR and sortilin.
    J Neurosci. 2005 Jun 1;25(22):5455-63 PMID: 15930396
  4. Sortilin is essential for proNGF-induced neuronal cell death.
    Nature. 2004 Feb 26;427(6977):843-8 PMID: 14985763
  5. The sortilin cytoplasmic tail conveys Golgi-endosome transport and binds the VHS domain of the GGA2 sorting protein.
    EMBO J. 2001 May 1;20(9):2180-90 PMID: 11331584
  6. The genes for the human VPS10 domain-containing receptors are large and contain many small exons.
    Hum Genet. 2001 Jun;108(6):529-36 PMID: 11499680
  7. Solubilization and purification of a high affinity neurotensin receptor from newborn human brain.
    Brain Res. 1994 Mar 14;639(2):245-52 PMID: 8205478
  8. Genetic analysis of the hypothalamic neurotensin system.
    Neuropsychopharmacology. 2006 Mar;31(3):535-43 PMID: 16123747
  9. Molecular characterization of a novel human hybrid-type receptor that binds the alpha2-macroglobulin receptor-associated protein.
    J Biol Chem. 1996 Dec 6;271(49):31379-83 PMID: 8940146
  10. Structure of nerve growth factor complexed with the shared neurotrophin receptor p75.
    Science. 2004 May 7;304(5672):870-5 PMID: 15131306
  11. Functional roles of the NTS2 and NTS3 receptors.
    Peptides. 2006 Oct;27(10):2469-75 PMID: 16872720
  12. Molecular identification of a novel candidate sorting receptor purified from human brain by receptor-associated protein affinity chromatography.
    J Biol Chem. 1997 Feb 7;272(6):3599-605 PMID: 9013611
  13. Crystal structure of human dipeptidyl peptidase IV/CD26 in complex with a substrate analog.
    Nat Struct Biol. 2003 Jan;10(1):19-25 PMID: 12483204
  14. Roles for the pro-neurotrophin receptor sortilin in neuronal development, aging and brain injury.
    Nat Neurosci. 2007 Nov;10(11):1449-57 PMID: 17934455
  15. Neurotensin and neurotensin receptors.
    Trends Pharmacol Sci. 1999 Jul;20(7):302-9 PMID: 10390649
  16. Sortilin/neurotensin receptor-3 binds and mediates degradation of lipoprotein lipase.
    J Biol Chem. 1999 Mar 26;274(13):8832-6 PMID: 10085125
  17. Endocytosis of apolipoprotein A-V by members of the low density lipoprotein receptor and the VPS10p domain receptor families.
    J Biol Chem. 2008 Sep 19;283(38):25920-7 PMID: 18603531
  18. Intracellular sortilin expression pattern regulates proNGF-induced naturally occurring cell death during development.
    Cell Death Differ. 2007 Aug;14(8):1552-4 PMID: 17541425
  19. Propeptide cleavage conditions sortilin/neurotensin receptor-3 for ligand binding.
    EMBO J. 1999 Feb 1;18(3):595-604 PMID: 9927419
  20. The 100-kDa neurotensin receptor is gp95/sortilin, a non-G-protein-coupled receptor.
    J Biol Chem. 1998 Oct 9;273(41):26273-6 PMID: 9756851
  21. Functional organization of the sortilin Vps10p domain.
    J Biol Chem. 2004 Nov 26;279(48):50221-9 PMID: 15364913
Article Info
Journal
Nature structural & molecular biology
Abbr.
Nat Struct Mol Biol
ISSN
1545-9985
DOI
10.1038/nsmb.1543
Published
2009-01-00
Epub
2009-00-04
Pages
96-8
Language
English
Region
United States
NLM ID
101186374
Subset
IM
Databases
PDB
3F6K
External Links
PubMed source DOI: 10.1038/nsmb.1543 View journal details
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