SASDCZ5: Monomeric Sortilin at pH 7.4 (Sortilin 1 A464E alias Neurotensin-...

Basic information

• Entry: Database: SASBDB / ID: SASDCZ5

Sample

Monomeric Sortilin at pH 7.4

• Sortilin 1 A464E alias Neurotensin-receptor 3 A464E (protein), Mus musculus

Function / homology

Function:

neurotensin receptor activity, non-G protein-coupled / Golgi to lysosome transport / plasma membrane to endosome transport / myotube differentiation / nerve growth factor receptor activity / cerebellar climbing fiber to Purkinje cell synapse / maintenance of synapse structure / retromer complex binding / Golgi to endosome transport / endosome transport via multivesicular body sorting pathway / Golgi Associated Vesicle Biogenesis / nerve growth factor binding / vesicle organization / protein targeting to lysosome / trans-Golgi network transport vesicle / Golgi cisterna membrane / endosome to lysosome transport / negative regulation of fat cell differentiation / neurotrophin TRK receptor signaling pathway / D-glucose import / extrinsic apoptotic signaling pathway via death domain receptors / neuropeptide signaling pathway / clathrin-coated pit / ossification / cytoplasmic vesicle membrane / 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

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

• Model #1375: ; Type: mix / Radius of dummy atoms: 1.90 A / Chi-square value: 1.12 / P-value: 0.000015; Search similar-shape structures of this assembly by Omokage search (details)
• Model #1383: ; Type: dummy / Radius of dummy atoms: 2.20 A / Chi-square value: 0.658 / P-value: 0.029490; Search similar-shape structures of this assembly by Omokage search (details)

Sample

• Sample: Name: Monomeric Sortilin at pH 7.4 / Specimen concentration: 0.3 mg/ml
• Buffer: Name: 25 mM HEPES pH 7.4, 150 mM NaCl / pH: 7.4

Entity #734

Type: protein
Description: Sortilin 1 A464E alias Neurotensin-receptor 3 A464E
Formula weight: 76.499 / Num. of mol.: 1 / Source: Mus musculus / References: UniProt: Q6PHU5
Sequence:

GAPAEDQDCG RLPDFIAKLT NNTHQHVFDD LSGSVSLSWV GDSTGVILVL TTFQVPLVIV SFGQSKLYRS EDYGKNFKDI TNLINNTFIR TEFGMAIGPE NSGKVILTAE VSGGSRGGRV FRSSDFAKNF VQTDLPFHPL TQMMYSPQNS DYLLALSTEN GLWVSKNFGE KWEEIHKAVC LAKWGPNNII FFTTHVNGSC KADLGALELW RTSDLGKTFK TIGVKIYSFG LGGRFLFASV MADKDTTRRI HVSTDQGDTW SMAQLPSVGQ EQFYSILAAN EDMVFMHVDE PGDTGFGTIF TSDDRGIVYS KSLDRHLYTT TGGETDFTNV TSLRGVYITS TLSEDNSIQS MITFDQGGRW EHLRKPENSK CDATAKNKNE CSLHIHASYS ISQKLNVPMA PLSEPNAVGI VIAHGSVGDE ISVMVPDVYI SDDGGYSWAK MLEGPHYYTI LDSGGIIVAI EHSNRPINVI KFSTDEGQCW QSYVFTQEPI YFTGLASEPG ARSMNISIWG FTESFITRQW VSYTVDFKDI LERNCEEDDY TTWLAHSTDP GDYKDGCILG YKEQFLRLRK SSVCQNGRDY VVAKQPSVCP CSLEDFLCDF GYFRPENASE CVEQPELKGH ELEFCLYGKE EHLTTNGYRK IPGDKCQGGM NPAREVKDLK KKCTSNFLNP TKQNSKSAAA HHHHHH

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.: 2.87 mm
• Detector: Name: Pilatus 1M

Scan

Title: Monomeric Sortilin at pH 7.4 / Measurement date: Apr 17, 2016 / Storage temperature: 20 °C / Cell temperature: 20 °C / Exposure time: 1 sec. / Number of frames: 2600 / Unit: 1/nm /

	Min	Max
Q	0.0939	2.4987

Distance distribution function P(R)

Sofotware P(R): GNOM 5.0 / Number of points: 501 /

	Min	Max
Q	0.0939077	2.45158
P(R) point	1	501
R	0	10.5

Result

Type of curve: other

	Experimental	Standard	Standard error	Porod
MW	94 kDa	86 kDa	9	127 kDa
Volume	-	-	-	217 nm3

	P(R)	P(R) error	Guinier	Guinier error
Forward scattering, I0	25.2	0.06	25.14	0.04
Radius of gyration, Rg	3.29 nm	0.01	3.26 nm	0.04

	Min	Max
D	-	10.5
Guinier point	3	65