SASDCE7: Monomeric Sortilin at pH 7.4 in the presence of neurotensin

Basic information

Entry

Database: SASBDB / ID: SASDCE7

Sample

Monomeric Sortilin at pH 7.4 in the presence of neurotensin

• Sortilin, also: Neurotensin-receptor 3 (protein), Sort1, also: NTR3, Mus musculus

Function / homology

Function:

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

Domain/homology:

VPS10 / Sortilin, C-terminal / Sortilin, N-terminal / Sortilin, neurotensin receptor 3, C-terminal / Sortilin, neurotensin receptor 3, / VPS10 / WD40/YVTN repeat-like-containing domain superfamily

Component:

Sortilin

• 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 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

• Martha Brennich (European Molecular Biology Laboratory (EMBL) - Grenoble Outstation)

Models

Sample

• Sample: Name: Monomeric Sortilin at pH 7.4 in the presence of neurotensin
• 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 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.: 2.86 mm
• 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 /

	Min	Max
Q	0.1128	2.5035

Distance distribution function P(R)

Sofotware P(R): GNOM 5.0 / Number of points: 485 /

	Min	Max
Q	0.112769	2.395
P(R) point	1	485
R	0	11.67

Result

Type of curve: other
Comments: Number of frames used for averaging: unknown. Exposure time: unknown. Sample concentration: unknown.

	Experimental	Porod
MW	113 kDa	113 kDa
Volume	-	192 nm3

	P(R)	P(R) error	Guinier
Forward scattering, I0	33.8	0.09	33.7
Radius of gyration, Rg	3.37 nm	0.02	3.34 nm

	Min	Max
D	-	11.7
Guinier point	1	59