+Open data
-Basic information
Entry | Database: SASBDB / ID: SASDCE7 |
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Sample | Monomeric Sortilin at pH 7.4 in the presence of neurotensin
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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 / maintenance of synapse structure / retromer complex binding / Golgi to endosome transport / nerve growth factor receptor activity / endosome transport via multivesicular body sorting pathway ...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 / endosome transport via multivesicular body sorting pathway / vesicle organization / 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 / endosome to lysosome transport / negative regulation of fat cell differentiation / glucose import / neurotrophin TRK receptor signaling pathway / neuropeptide signaling pathway / extrinsic apoptotic signaling pathway via death domain receptors / ossification / clathrin-coated pit / response to insulin / cytoplasmic vesicle membrane / endocytosis / regulation of gene expression / nuclear membrane / endosome membrane / early endosome / lysosome / lysosomal membrane / neuronal cell body / dendrite / endoplasmic reticulum membrane / perinuclear region of cytoplasm / enzyme binding / cell surface / Golgi apparatus / membrane / 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
-Downloads & links
-Data source
SASBDB page | SASDCE7 |
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-Related structure data
Related structure data | 5nmrC 5nmtC 5nniC 5nnjC C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-External links
Related items in Molecule of the Month |
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-Models
-Sample
Sample | Name: Monomeric Sortilin at pH 7.4 in the presence of neurotensin |
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Buffer | Name: 25 mM HEPES pH 7.4, 150 mM NaCl / pH: 7.4 |
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 synchrotron / Wavelength: 0.099 Å / Dist. spec. to detc.: 2.86 mm | ||||||||||||||||||||||||||||||
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Detector | Name: Pilatus 1M | ||||||||||||||||||||||||||||||
Scan | Title: Monomeric Sortilin at pH 7.4 in the presence of neurotensin Measurement date: Apr 17, 2016 / Cell temperature: 20 °C / Unit: 1/nm /
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Distance distribution function P(R) | Sofotware P(R): GNOM 5.0 / Number of points: 485 /
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Result | Type of curve: other Comments: Number of frames used for averaging: unknown. Exposure time: unknown. Sample concentration: unknown.
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