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Yorodumi- SASDCY5: Dimeric Sortilin at pH 5.5 (Sortilin, also: Neurotensin-receptor ... -
+Open data
-Basic information
Entry | Database: SASBDB / ID: SASDCY5 |
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Sample | Dimeric Sortilin at pH 5.5
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Function / homology | Function and homology information 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 / retromer complex binding / maintenance of synapse structure / 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 / retromer complex binding / maintenance of synapse structure / 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 / negative regulation of fat cell differentiation / Golgi cisterna membrane / 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 | Mus musculus (house mouse) |
Citation | Journal: Nat Commun / Year: 2017 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. |
Contact author |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Data source
SASBDB page | SASDCY5 |
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-Related structure data
-External links
Related items in Molecule of the Month |
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-Models
Model #1381 | Type: mix / Radius of dummy atoms: 1.90 A / Chi-square value: 0.73 / P-value: 0.627300 Search similar-shape structures of this assembly by Omokage search (details) |
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Model #1382 | Type: dummy / Radius of dummy atoms: 2.30 A / Chi-square value: 0.695 / P-value: 0.178200 Search similar-shape structures of this assembly by Omokage search (details) |
-Sample
Sample | Name: Dimeric Sortilin at pH 5.5 / Specimen concentration: 0.62 mg/ml |
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Buffer | Name: 25 mM MES pH 5.5, 150 mM NaCl / pH: 5.5 |
Entity #733 | Name: Sort1, also: NTR3 / Type: protein / Description: Sortilin, also: Neurotensin-receptor 3 / Formula weight: 76.585 / Num. of mol.: 2 / Source: Mus musculus / References: UniProt: Q6PHU5 Sequence: GSGAPAEDQD CGRLPDFIAK LTNNTHQHVF DDLSGSVSLS WVGDSTGVIL VLTTFQVPLV IVSFGQSKLY RSEDYGKNFK DITNLINNTF IRTEFGMAIG PENSGKVILT AEVSGGSRGG RVFRSSDFAK NFVQTDLPFH PLTQMMYSPQ NSDYLLALST ENGLWVSKNF ...Sequence: GSGAPAEDQD CGRLPDFIAK LTNNTHQHVF DDLSGSVSLS WVGDSTGVIL VLTTFQVPLV IVSFGQSKLY RSEDYGKNFK DITNLINNTF IRTEFGMAIG PENSGKVILT AEVSGGSRGG RVFRSSDFAK NFVQTDLPFH PLTQMMYSPQ NSDYLLALST ENGLWVSKNF GEKWEEIHKA VCLAKWGPNN IIFFTTHVNG SCKADLGALE LWRTSDLGKT FKTIGVKIYS FGLGGRFLFA SVMADKDTTR RIHVSTDQGD TWSMAQLPSV GQEQFYSILA ANEDMVFMHV DEPGDTGFGT IFTSDDRGIV YSKSLDRHLY TTTGGETDFT NVTSLRGVYI TSTLSEDNSI QSMITFDQGG RWEHLRKPEN SKCDATAKNK NECSLHIHAS YSISQKLNVP MAPLSEPNAV GIVIAHGSVG DAISVMVPDV YISDDGGYSW AKMLEGPHYY TILDSGGIIV AIEHSNRPIN VIKFSTDEGQ CWQSYVFTQE PIYFTGLASE PGARSMNISI WGFTESFITR QWVSYTVDFK DILERNCEED DYTTWLAHST DPGDYKDGCI LGYKEQFLRL RKSSVCQNGR DYVVAKQPSV CPCSLEDFLC DFGYFRPENA SECVEQPELK GHELEFCLYG KEEHLTTNGY RKIPGDKCQG GMNPAREVKD LKKKCTSNFL NPTKQNSKSA AAHHHHHH |
-Experimental information
Beam | Instrument name: ESRF BM29 / City: Grenoble / 国: France / Type of source: X-ray synchrotronSynchrotron / Wavelength: 0.099 Å / Dist. spec. to detc.: 2.87 mm | |||||||||||||||||||||||||||||||||||||||
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Detector | Name: Pilatus 1M | |||||||||||||||||||||||||||||||||||||||
Scan | Title: Dimeric Sortilin at pH 5.5 / Measurement date: Apr 17, 2016 / Storage temperature: 20 °C / Cell temperature: 20 °C / Exposure time: 1 sec. / Number of frames: 2600 / Unit: 1/nm /
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Distance distribution function P(R) | Sofotware P(R): GNOM 5.0 / Number of points: 410 /
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Result | Type of curve: other
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