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- EMDB-54402: Structure of in-vivo formed alpha-synuclein fibrils purified from... -
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Open data
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Basic information
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Title | Structure of in-vivo formed alpha-synuclein fibrils purified from a M83+/- mouse brain injected with recombinant 1B fibrils | |||||||||
![]() | Postprocessed EM map | |||||||||
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![]() | Alpha-synuclein / Prion-like / Fibril / Paired helical filament / PROTEIN FIBRIL | |||||||||
Function / homology | ![]() PKR-mediated signaling / regulation of neurotransmitter secretion / platelet alpha granule membrane / membrane organization / synaptic transmission, dopaminergic / neurotransmitter secretion / neutral lipid metabolic process / regulation of acyl-CoA biosynthetic process / negative regulation of dopamine uptake involved in synaptic transmission / negative regulation of norepinephrine uptake ...PKR-mediated signaling / regulation of neurotransmitter secretion / platelet alpha granule membrane / membrane organization / synaptic transmission, dopaminergic / neurotransmitter secretion / neutral lipid metabolic process / regulation of acyl-CoA biosynthetic process / negative regulation of dopamine uptake involved in synaptic transmission / negative regulation of norepinephrine uptake / response to desipramine / positive regulation of SNARE complex assembly / positive regulation of hydrogen peroxide catabolic process / supramolecular fiber / mitochondrial membrane organization / negative regulation of chaperone-mediated autophagy / negative regulation of platelet-derived growth factor receptor signaling pathway / positive regulation of protein localization to cell periphery / negative regulation of exocytosis / regulation of glutamate secretion / arachidonate binding / SNARE complex assembly / regulation of reactive oxygen species metabolic process / positive regulation of neurotransmitter secretion / dopamine biosynthetic process / response to iron(II) ion / positive regulation of inositol phosphate biosynthetic process / regulation of locomotion / negative regulation of dopamine metabolic process / regulation of macrophage activation / synaptic vesicle priming / transporter regulator activity / negative regulation of microtubule polymerization / synaptic vesicle transport / positive regulation of receptor recycling / mitochondrial ATP synthesis coupled electron transport / dynein complex binding / regulation of dopamine secretion / negative regulation of thrombin-activated receptor signaling pathway / dopamine metabolic process / cuprous ion binding / protein complex oligomerization / nuclear outer membrane / positive regulation of exocytosis / response to magnesium ion / positive regulation of endocytosis / kinesin binding / synaptic vesicle endocytosis / cysteine-type endopeptidase inhibitor activity / negative regulation of serotonin uptake / regulation of neuronal synaptic plasticity / regulation of presynapse assembly / response to type II interferon / alpha-tubulin binding / positive regulation of synaptic transmission / beta-tubulin binding / phospholipase binding / behavioral response to cocaine / cellular response to copper ion / phospholipid metabolic process / cellular response to fibroblast growth factor stimulus / inclusion body / axon terminus / Hsp70 protein binding / response to interleukin-1 / regulation of microtubule cytoskeleton organization / SNARE binding / positive regulation of release of sequestered calcium ion into cytosol / adult locomotory behavior / excitatory postsynaptic potential / phosphoprotein binding / protein tetramerization / fatty acid metabolic process / microglial cell activation / regulation of long-term neuronal synaptic plasticity / synapse organization / ferrous iron binding / protein destabilization / phospholipid binding / receptor internalization / tau protein binding / long-term synaptic potentiation / terminal bouton / positive regulation of inflammatory response / synaptic vesicle membrane / actin cytoskeleton / actin binding / growth cone / cellular response to oxidative stress / cell cortex / neuron apoptotic process / response to lipopolysaccharide / microtubule binding / chemical synaptic transmission / histone binding / negative regulation of neuron apoptotic process / mitochondrial outer membrane / cytoskeleton / oxidoreductase activity / postsynapse Similarity search - Function | |||||||||
Biological species | ![]() ![]() | |||||||||
Method | helical reconstruction / cryo EM / Resolution: 3.8 Å | |||||||||
![]() | van den Heuvel L / Burger D / Kashyrina M / de La Seigliere H / Lewis AJ / De Nuccio F / Mohammed I / Verchere J / Feuillie C / Berbon M ...van den Heuvel L / Burger D / Kashyrina M / de La Seigliere H / Lewis AJ / De Nuccio F / Mohammed I / Verchere J / Feuillie C / Berbon M / Arotcarena M / Retailleau A / Bezard E / Canron M / Meissner WG / Loquet A / Bousset L / Poujol C / Nilsson KPR / Laferriere F / Baron T / Lofrumento DD / De Giorgi F / Stahlberg H / Ichas F | |||||||||
Funding support | ![]() ![]()
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![]() | ![]() Title: Synthetic alpha-synuclein fibrils replicate in mice causing MSA neuropathology Authors: Burger D / Kashyrina M / van den Heuvel L / de La Seigliere H / Lewis AJ / De Nuccio F / Mohammed I / Verchere J / Feuillie C / Berbon M / Arotcarena M / Retailleau A / Bezard E / Canron M / ...Authors: Burger D / Kashyrina M / van den Heuvel L / de La Seigliere H / Lewis AJ / De Nuccio F / Mohammed I / Verchere J / Feuillie C / Berbon M / Arotcarena M / Retailleau A / Bezard E / Canron M / Meissner WG / Loquet A / Bousset L / Poujol C / Nilsson KPR / Laferriere F / Baron T / Lofrumento DD / De Giorgi F / Stahlberg H / Ichas F | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 14.4 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 24.6 KB 24.6 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 14.1 KB | Display | ![]() |
Images | ![]() | 109.7 KB | ||
Masks | ![]() | 244.1 MB | ![]() | |
Filedesc metadata | ![]() | 7 KB | ||
Others | ![]() ![]() ![]() | 12.1 MB 194.9 MB 194.8 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 922.8 KB | Display | ![]() |
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Full document | ![]() | 922.5 KB | Display | |
Data in XML | ![]() | 21.7 KB | Display | |
Data in CIF | ![]() | 28.9 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 9rzfMC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Map
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Annotation | Postprocessed EM map | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.464 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
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Projections & Slices |
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Density Histograms |
-Additional map: Helically symmetrized EM map
File | emd_54402_additional_1.map | ||||||||||||
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Annotation | Helically symmetrized EM map | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half map 2 of refinement (unfiltered)
File | emd_54402_half_map_1.map | ||||||||||||
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Annotation | Half map 2 of refinement (unfiltered) | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half map 1 of refinement (unfiltered)
File | emd_54402_half_map_2.map | ||||||||||||
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Annotation | Half map 1 of refinement (unfiltered) | ||||||||||||
Projections & Slices |
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Density Histograms |
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Sample components
-Entire : Alpha-synuclein fibril purified from the brain of a 1B-injected M...
Entire | Name: Alpha-synuclein fibril purified from the brain of a 1B-injected M83+/- mouse |
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Components |
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-Supramolecule #1: Alpha-synuclein fibril purified from the brain of a 1B-injected M...
Supramolecule | Name: Alpha-synuclein fibril purified from the brain of a 1B-injected M83+/- mouse type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 14 kDa/nm |
-Macromolecule #1: Alpha-synuclein
Macromolecule | Name: Alpha-synuclein / type: protein_or_peptide / ID: 1 / Details: A53T / Number of copies: 6 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 6.037906 KDa |
Sequence | String: VLYVGSKTKE GVVHGVTTVA EKTKEQVTNV GGAVVTGVTA VAQKTVEGAG SIAAATGFVK K UniProtKB: Alpha-synuclein |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | helical reconstruction |
Aggregation state | filament |
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Sample preparation
Buffer | pH: 7.4 Component:
Details: 50 mM Tris-HCl, 150 mM NaCl, pH7.4 | |||||||||
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Grid | Model: Quantifoil / Material: GOLD / Mesh: 300 / Support film - #0 - Film type ID: 1 / Support film - #0 - Material: CARBON / Support film - #0 - topology: HOLEY ARRAY / Support film - #0 - Film thickness: 12 / Support film - #1 - Film type ID: 2 / Support film - #1 - Material: CARBON / Support film - #1 - topology: CONTINUOUS / Support film - #1 - Film thickness: 5 / Details: The grids were not glow-discharged | |||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 80 % / Chamber temperature: 293 K / Instrument: LEICA EM GP | |||||||||
Details | Sarkosyl-insoluble fraction |
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Electron microscopy
Microscope | TFS KRIOS |
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Specialist optics | Energy filter - Name: TFS Selectris X |
Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Digitization - Dimensions - Width: 4096 pixel / Digitization - Dimensions - Height: 4096 pixel / Number grids imaged: 2 / Number real images: 42812 / Average exposure time: 3.04 sec. / Average electron dose: 50.0 e/Å2 Details: Images were collected in movie-mode with a total of 936 frames per movie. |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | C2 aperture diameter: 50.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 2.2 µm / Nominal defocus min: 0.8 µm / Nominal magnification: 165000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
-Atomic model buiding 1
Initial model |
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Details | A rigid-body fit was done using ChimeraX and a subsequent jiggle fit and all-atom refinement was done in Coot. | ||||||
Refinement | Space: REAL / Protocol: FLEXIBLE FIT | ||||||
Output model | ![]() PDB-9rzf: |