+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-3841 | |||||||||
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Title | Negative-stain surface of low-pH sortilin dimer | |||||||||
Map data | Negative-stain surface of low-pH sortilin dimer | |||||||||
Sample |
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Function / homology | Function and homology information neurotensin receptor activity, non-G protein-coupled / negative regulation of lipoprotein lipase activity / 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 / Golgi to lysosome transport ...neurotensin receptor activity, non-G protein-coupled / negative regulation of lipoprotein lipase activity / 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 / Golgi to lysosome transport / endosome transport via multivesicular body sorting pathway / vesicle organization / nerve growth factor binding / protein targeting to lysosome / trans-Golgi network transport vesicle / clathrin-coated vesicle / negative regulation of fat cell differentiation / Golgi cisterna membrane / Golgi Associated Vesicle Biogenesis / 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 / endocytosis / cytoplasmic vesicle / regulation of gene expression / nuclear membrane / lysosome / early endosome / endosome membrane / G protein-coupled receptor signaling pathway / lysosomal membrane / endoplasmic reticulum membrane / perinuclear region of cytoplasm / Golgi apparatus / enzyme binding / cell surface / membrane / plasma membrane / cytosol Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / negative staining / Resolution: 13.0 Å | |||||||||
Authors | Januliene D / Thirup S / Moeller A | |||||||||
Citation | Journal: Structure / Year: 2017 Title: Acidic Environment Induces Dimerization and Ligand Binding Site Collapse in the Vps10p Domain of Sortilin. Authors: Dovile Januliene / Jacob Lauwring Andersen / Jeppe Achton Nielsen / Esben Meldgaard Quistgaard / Maria Hansen / Dorthe Strandbygaard / Arne Moeller / Claus Munck Petersen / Peder Madsen / Søren Skou Thirup / Abstract: Sortilin is a neuronal receptor involved in transmembrane signaling, endocytosis, and intracellular sorting of proteins. It cycles through a number of cellular compartments where it encounters ...Sortilin is a neuronal receptor involved in transmembrane signaling, endocytosis, and intracellular sorting of proteins. It cycles through a number of cellular compartments where it encounters various acidic conditions. The crystal structure of the sortilin ectodomain has previously been determined at neutral pH. Here, we present the 3.5-Å resolution crystal structure of sortilin at pH 5.5, which represents an environment similar to that of late endosomes, where ligands are released. The structure reveals an overall distortion of the 10-bladed β-propeller domain. This distortion and specific conformational changes, caused by protonation of a number of histidine residues, render the currently known binding sites unavailable for ligand binding. Access to the binding sites is furthermore blocked by a reversible and pH-dependent formation of tight sortilin dimers, also confirmed by electron microscopy, size-exclusion chromatography, and mutational studies. This study reveals how sortilin binding sites are disrupted and explains pH-dependent ligand affinity. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_3841.map.gz | 318.9 KB | EMDB map data format | |
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Header (meta data) | emd-3841-v30.xml emd-3841.xml | 8.6 KB 8.6 KB | Display Display | EMDB header |
Images | emd_3841.png | 24.4 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-3841 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-3841 | HTTPS FTP |
-Related structure data
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_3841.map.gz / Format: CCP4 / Size: 251 KB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Negative-stain surface of low-pH sortilin dimer | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 3.15 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Sample components
-Entire : Low-pH-induced dimer of human sSortilin extracellular domain
Entire | Name: Low-pH-induced dimer of human sSortilin extracellular domain |
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Components |
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-Supramolecule #1: Low-pH-induced dimer of human sSortilin extracellular domain
Supramolecule | Name: Low-pH-induced dimer of human sSortilin extracellular domain type: complex / ID: 1 / Parent: 0 |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Homo sapiens (human) / Recombinant cell: HEK |
Molecular weight | Experimental: 200 KDa |
-Experimental details
-Structure determination
Method | negative staining |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 0.01 mg/mL |
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Buffer | pH: 5.5 |
Staining | Type: NEGATIVE / Material: Uranyl Formate |
-Electron microscopy
Microscope | FEI TECNAI SPIRIT |
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Electron beam | Acceleration voltage: 120 kV / Electron source: LAB6 |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy |
Image recording | Film or detector model: TVIPS TEMCAM-F416 (4k x 4k) / Average electron dose: 8.0 e/Å2 |
Experimental equipment | Model: Tecnai Spirit / Image courtesy: FEI Company |
-Image processing
CTF correction | Software - Name: CTFFIND (ver. 3) |
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Initial angle assignment | Type: ANGULAR RECONSTITUTION |
Final angle assignment | Type: ANGULAR RECONSTITUTION |
Final reconstruction | Applied symmetry - Point group: C1 (asymmetric) / Resolution.type: BY AUTHOR / Resolution: 13.0 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: RELION (ver. 2.0) / Number images used: 55967 |