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- PDB-5nnj: Dimer structure of Sortilin ectodomain crystal form 3, 4.0 Angstrom -
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Open data
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Basic information
Entry | Database: PDB / ID: 5nnj | |||||||||
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Title | Dimer structure of Sortilin ectodomain crystal form 3, 4.0 Angstrom | |||||||||
![]() | Sortilin | |||||||||
![]() | TRANSPORT PROTEIN / transport receptor / VPS10 domain | |||||||||
Function / homology | ![]() neurotensin receptor activity, non-G protein-coupled / Golgi to lysosome transport / myotube differentiation / cerebellar climbing fiber to Purkinje cell synapse / plasma membrane to endosome transport / maintenance of synapse structure / retromer complex binding / Golgi to endosome transport / nerve growth factor receptor activity / vesicle organization ...neurotensin receptor activity, non-G protein-coupled / Golgi to lysosome transport / myotube differentiation / cerebellar climbing fiber to Purkinje cell synapse / plasma membrane to endosome transport / maintenance of synapse structure / retromer complex binding / Golgi to endosome transport / nerve growth factor receptor activity / vesicle organization / endosome transport via multivesicular body sorting pathway / Golgi Associated Vesicle Biogenesis / nerve growth factor binding / protein targeting to lysosome / trans-Golgi network transport vesicle / positive regulation of epithelial cell apoptotic process / Golgi cisterna membrane / negative regulation of fat cell differentiation / endosome to lysosome transport / glucose import / neurotrophin TRK receptor signaling pathway / extrinsic apoptotic signaling pathway via death domain receptors / neuropeptide signaling pathway / clathrin-coated pit / ossification / response to insulin / cytoplasmic vesicle membrane / endocytosis / regulation of gene expression / nuclear membrane / lysosome / early endosome / endosome membrane / lysosomal membrane / neuronal cell body / dendrite / endoplasmic reticulum membrane / perinuclear region of cytoplasm / Golgi apparatus / enzyme binding / cell surface / plasma membrane / cytosol Similarity search - Function | |||||||||
Biological species | ![]() ![]() | |||||||||
Method | ![]() ![]() ![]() | |||||||||
![]() | Leloup, N.O.L. / Janssen, B.J.C. | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Low pH-induced conformational change and dimerization of sortilin triggers endocytosed ligand release. Authors: Nadia Leloup / Philip Lössl / Dimphna H Meijer / Martha Brennich / Albert J R Heck / Dominique M E Thies-Weesie / Bert J C Janssen / ![]() ![]() Abstract: Low pH-induced ligand release and receptor recycling are important steps for endocytosis. The transmembrane protein sortilin, a β-propeller containing endocytosis receptor, internalizes a diverse ...Low pH-induced ligand release and receptor recycling are important steps for endocytosis. The transmembrane protein sortilin, a β-propeller containing endocytosis receptor, internalizes a diverse set of ligands with roles in cell differentiation and homeostasis. The molecular mechanisms of pH-mediated ligand release and sortilin recycling are unresolved. Here we present crystal structures that show the sortilin luminal segment (s-sortilin) undergoes a conformational change and dimerizes at low pH. The conformational change, within all three sortilin luminal domains, provides an altered surface and the dimers sterically shield a large interface while bringing the two s-sortilin C-termini into close proximity. Biophysical and cell-based assays show that members of two different ligand families, (pro)neurotrophins and neurotensin, preferentially bind the sortilin monomer. This indicates that sortilin dimerization and conformational change discharges ligands and triggers recycling. More generally, this work may reveal a double mechanism for low pH-induced ligand release by endocytosis receptors. | |||||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 1 MB | Display | ![]() |
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PDB format | ![]() | 906.9 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
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-Validation report
Summary document | ![]() | 2.2 MB | Display | ![]() |
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Full document | ![]() | 2.3 MB | Display | |
Data in XML | ![]() | 93.3 KB | Display | |
Data in CIF | ![]() | 123.8 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 5nmrC ![]() 5nmtSC ![]() 5nniC S: Starting model for refinement C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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1 | ![]()
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2 | ![]()
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Unit cell |
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Components
#1: Protein | Mass: 81364.078 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #2: Polysaccharide | beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta- ...beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source #3: Sugar | ChemComp-NAG / |
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-Experimental details
-Experiment
Experiment | Method: ![]() |
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Sample preparation
Crystal | Density Matthews: 2.85 Å3/Da / Density % sol: 56.89 % |
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Crystal grow | Temperature: 291 K / Method: vapor diffusion, sitting drop / pH: 6.2 Details: 0.18 M Magnesium formate dihydrate pH 7.0, 18% PEG 3350 (w/v), 1 mM CaCl2 and 1 mM GSH (L-Glutathione reduced) & GSSG (L-Glutathione oxidized), final pH 6.2 |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: ![]() ![]() ![]() |
Detector | Type: DECTRIS PILATUS 6M-F / Detector: PIXEL / Date: Feb 14, 2014 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.97599 Å / Relative weight: 1 |
Reflection | Resolution: 4→71.72 Å / Num. obs: 32164 / % possible obs: 100 % / Redundancy: 12 % / CC1/2: 0.998 / Rmerge(I) obs: 0.03936 / Rpim(I) all: 0.03936 / Rrim(I) all: 0.05567 / Net I/σ(I): 7.7 |
Reflection shell | Resolution: 4→4.143 Å / Redundancy: 2 % / Rmerge(I) obs: 0.4076 / Mean I/σ(I) obs: 1.83 / Num. unique obs: 3145 / CC1/2: 0.789 / Rpim(I) all: 0.4076 / Rrim(I) all: 0.5765 / % possible all: 99.71 |
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Processing
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Refinement | Method to determine structure: ![]() Starting model: 5NMT Resolution: 4→71.719 Å / SU ML: 0.5 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 27.61 / Stereochemistry target values: ML
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 4→71.719 Å
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Refine LS restraints |
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LS refinement shell |
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Refinement TLS params. | Method: refined / Refine-ID: X-RAY DIFFRACTION
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Refinement TLS group |
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