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Open data
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Basic information
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![]() | Dimeric Sortilin at pH 7.4 in the presence of neurotensin
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Function / homology | ![]() neurotensin receptor activity, non-G protein-coupled / myotube differentiation / Golgi to lysosome transport / plasma membrane to endosome transport / cerebellar climbing fiber to Purkinje cell synapse / maintenance of synapse structure / nerve growth factor receptor activity / Golgi to endosome transport / retromer complex binding / endosome transport via multivesicular body sorting pathway ...neurotensin receptor activity, non-G protein-coupled / myotube differentiation / Golgi to lysosome transport / plasma membrane to endosome transport / cerebellar climbing fiber to Purkinje cell synapse / maintenance of synapse structure / nerve growth factor receptor activity / Golgi to endosome transport / retromer complex binding / endosome transport via multivesicular body sorting pathway / Golgi Associated Vesicle Biogenesis / vesicle organization / nerve growth factor binding / trans-Golgi network transport vesicle / protein targeting to lysosome / Golgi cisterna membrane / endosome to lysosome transport / negative regulation of fat cell differentiation / D-glucose import / neurotrophin TRK receptor signaling pathway / extrinsic apoptotic signaling pathway via death domain receptors / neuropeptide signaling pathway / clathrin-coated pit / cytoplasmic vesicle membrane / ossification / response to insulin / endocytosis / regulation of gene expression / nuclear membrane / early endosome / lysosome / endosome membrane / lysosomal membrane / endoplasmic reticulum membrane / perinuclear region of cytoplasm / enzyme binding / cell surface / Golgi apparatus / plasma membrane / cytosol Similarity search - Function |
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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. |
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Structure visualization
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Downloads & links
-Data source
SASBDB page | ![]() |
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-Related structure data
Related structure data | ![]() 5nmrC ![]() 5nmtC ![]() 5nniC ![]() 5nnjC C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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External links
Related items in Molecule of the Month |
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-Models
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Sample
![]() | Name: Dimeric 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 ![]() | |||||||||||||||||||||||||||||||||
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Detector | Name: Pilatus 1M | |||||||||||||||||||||||||||||||||
Scan | Measurement date: Apr 17, 2016 / Cell temperature: 20 °C / Unit: 1/nm /
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Distance distribution function P(R) |
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Result | Comments: Number of frames used for averaging: unknown. Exposure time: unknown. Sample concentration: unknown.
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