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Yorodumi- PDB-8oqy: Structure of apo form of human gamma-secretase PSEN1 APH-1B isofo... -
+Open data
-Basic information
Entry | Database: PDB / ID: 8oqy | |||||||||||||||
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Title | Structure of apo form of human gamma-secretase PSEN1 APH-1B isoform reconstituted into lipid nanodisc | |||||||||||||||
Components |
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Keywords | MEMBRANE PROTEIN / intramembrane proteolysis / protease / di-aspartyl protease / Alzheimer's disease / complex | |||||||||||||||
Function / homology | Function and homology information Cajal-Retzius cell differentiation / positive regulation of L-glutamate import across plasma membrane / amyloid precursor protein biosynthetic process / positive regulation of coagulation / protein catabolic process at postsynapse / negative regulation of core promoter binding / gamma-secretase complex / aspartic endopeptidase activity, intramembrane cleaving / short-term synaptic potentiation / positive regulation of amyloid precursor protein biosynthetic process ...Cajal-Retzius cell differentiation / positive regulation of L-glutamate import across plasma membrane / amyloid precursor protein biosynthetic process / positive regulation of coagulation / protein catabolic process at postsynapse / negative regulation of core promoter binding / gamma-secretase complex / aspartic endopeptidase activity, intramembrane cleaving / short-term synaptic potentiation / positive regulation of amyloid precursor protein biosynthetic process / Noncanonical activation of NOTCH3 / positive regulation of endopeptidase activity / choline transport / Notch receptor processing / sequestering of calcium ion / central nervous system myelination / synaptic vesicle targeting / membrane protein intracellular domain proteolysis / negative regulation of axonogenesis / regulation of resting membrane potential / T cell activation involved in immune response / NOTCH4 Activation and Transmission of Signal to the Nucleus / skin morphogenesis / growth factor receptor binding / neural retina development / dorsal/ventral neural tube patterning / regulation of synaptic vesicle cycle / L-glutamate import across plasma membrane / myeloid dendritic cell differentiation / Regulated proteolysis of p75NTR / regulation of phosphorylation / locomotion / brain morphogenesis / glutamate receptor signaling pathway / endoplasmic reticulum calcium ion homeostasis / nuclear outer membrane / smooth endoplasmic reticulum calcium ion homeostasis / amyloid precursor protein metabolic process / astrocyte activation involved in immune response / regulation of canonical Wnt signaling pathway / aggresome / regulation of long-term synaptic potentiation / embryonic limb morphogenesis / skeletal system morphogenesis / cell fate specification / regulation of postsynapse organization / ciliary rootlet / myeloid cell homeostasis / azurophil granule membrane / dopamine receptor signaling pathway / Hydrolases; Acting on peptide bonds (peptidases); Aspartic endopeptidases / Golgi cisterna membrane / positive regulation of amyloid fibril formation / adult behavior / positive regulation of receptor recycling / positive regulation of dendritic spine development / mitochondrial transport / positive regulation of catalytic activity / regulation of neuron projection development / heart looping / blood vessel development / amyloid precursor protein catabolic process / cerebral cortex cell migration / smooth endoplasmic reticulum / protein glycosylation / amyloid-beta formation / autophagosome assembly / negative regulation of apoptotic signaling pathway / membrane protein ectodomain proteolysis / endopeptidase activator activity / EPH-ephrin mediated repulsion of cells / neuron development / rough endoplasmic reticulum / hematopoietic progenitor cell differentiation / somitogenesis / amyloid-beta metabolic process / T cell proliferation / Nuclear signaling by ERBB4 / Notch signaling pathway / negative regulation of ubiquitin-dependent protein catabolic process / regulation of synaptic transmission, glutamatergic / transport vesicle / NOTCH2 Activation and Transmission of Signal to the Nucleus / cellular response to calcium ion / neuron projection maintenance / Degradation of the extracellular matrix / NRIF signals cell death from the nucleus / Activated NOTCH1 Transmits Signal to the Nucleus / positive regulation of glycolytic process / cerebellum development / post-embryonic development / thymus development / dendritic shaft / negative regulation of protein phosphorylation / epithelial cell proliferation / PDZ domain binding / NOTCH3 Activation and Transmission of Signal to the Nucleus / astrocyte activation / apoptotic signaling pathway / synapse organization Similarity search - Function | |||||||||||||||
Biological species | Homo sapiens (human) | |||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.3 Å | |||||||||||||||
Authors | Odorcic, I. / Chavez Gutierrez, L. / Efremov, R.G. | |||||||||||||||
Funding support | Belgium, 4items
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Citation | Journal: To Be Published Title: Complex of human APH-1B isoform of gamma-secretase with Amyloid-beta in lipid environment suggests substrate shifting as the mechanism of sequential cleavage Authors: Odorcic, I. | |||||||||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8oqy.cif.gz | 239.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8oqy.ent.gz | 184.5 KB | Display | PDB format |
PDBx/mmJSON format | 8oqy.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/oq/8oqy ftp://data.pdbj.org/pub/pdb/validation_reports/oq/8oqy | HTTPS FTP |
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-Related structure data
Related structure data | 17112MC 8oqzC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-Protein , 2 types, 2 molecules AB
#1: Protein | Mass: 79371.586 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: NCSTN, KIAA0253, UNQ1874/PRO4317 / Cell line (production host): BTI-TN5B1-4 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: Q92542 |
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#2: Protein | Mass: 52713.535 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PSEN1, AD3, PS1, PSNL1 / Cell line (production host): BTI-TN5B1-4 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: P49768 |
-Gamma-secretase subunit ... , 2 types, 2 molecules CD
#3: Protein | Mass: 28480.844 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: APH1B, PSFL, UNQ688/PRO1328 / Cell line (production host): BTI-TN5B1-4 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: Q8WW43 |
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#4: Protein | Mass: 12038.029 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PSENEN, PEN2, MDS033 / Cell line (production host): BTI-TN5B1-4 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: Q9NZ42 |
-Sugars , 3 types, 11 molecules
#5: Polysaccharide | #6: Polysaccharide | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta- ...2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose | Source method: isolated from a genetically manipulated source #7: Sugar | ChemComp-NAG / |
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-Non-polymers , 1 types, 3 molecules
#8: Chemical |
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-Details
Has ligand of interest | N |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: Gamma secretase / Type: COMPLEX / Entity ID: #1-#4 / Source: RECOMBINANT | |||||||||||||||
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Molecular weight | Value: 0.172 MDa / Experimental value: NO | |||||||||||||||
Source (natural) | Organism: Homo sapiens (human) | |||||||||||||||
Source (recombinant) | Organism: Trichoplusia ni (cabbage looper) / Cell: BTI-TN5B1-4 | |||||||||||||||
Buffer solution | pH: 7.4 | |||||||||||||||
Buffer component |
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Specimen | Conc.: 0.04 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | |||||||||||||||
Specimen support | Grid material: COPPER / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil R0.6/1 | |||||||||||||||
Vitrification | Instrument: GATAN CRYOPLUNGE 3 / Cryogen name: ETHANE / Humidity: 92 % / Chamber temperature: 296 K |
-Electron microscopy imaging
Microscopy | Model: JEOL CRYO ARM 300 |
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Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELDBright-field microscopy / Nominal magnification: 60000 X / Nominal defocus max: 2000 nm / Nominal defocus min: 1200 nm / Calibrated defocus min: 1000 nm / Calibrated defocus max: 3000 nm / Cs: 2.55 mm / C2 aperture diameter: 100 µm / Alignment procedure: COMA FREE |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: JEOL CRYOSPECPORTER |
Image recording | Average exposure time: 3 sec. / Electron dose: 61 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) / Num. of grids imaged: 1 / Num. of real images: 10733 |
EM imaging optics | Energyfilter name: In-column Omega Filter / Energyfilter slit width: 20 eV |
Image scans | Width: 5760 / Height: 4092 |
-Processing
Software | Name: PHENIX / Version: 1.19.2_4158: / Classification: refinement | ||||||||||||||||||||||||||||||||||||||||
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EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 986830 | ||||||||||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 111197 / Algorithm: FOURIER SPACE / Num. of class averages: 1 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||||||||||
Atomic model building | Protocol: FLEXIBLE FIT / Space: REAL | ||||||||||||||||||||||||||||||||||||||||
Atomic model building | 3D fitting-ID: 1
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Refinement | Cross valid method: NONE Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 54.75 Å2 | ||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
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