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Yorodumi- EMDB-18990: CryoEM map of tau PHF sarkosyl-extracted from a human AD patient ... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-18990 | |||||||||||||||
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Title | CryoEM map of tau PHF sarkosyl-extracted from a human AD patient (associated with in situ tomography) | |||||||||||||||
Map data | Postprocessed sharpened map of tau PHF fibrils extracted from AD patient brain | |||||||||||||||
Sample |
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Keywords | Amyloid / Alzheimer's / tauopathy / fibril / filament / helical / PROTEIN FIBRIL | |||||||||||||||
Function / homology | Function and homology information plus-end-directed organelle transport along microtubule / axonal transport / histone-dependent DNA binding / neurofibrillary tangle assembly / positive regulation of diacylglycerol kinase activity / negative regulation of establishment of protein localization to mitochondrion / neurofibrillary tangle / positive regulation of protein localization to synapse / microtubule lateral binding / tubulin complex ...plus-end-directed organelle transport along microtubule / axonal transport / histone-dependent DNA binding / neurofibrillary tangle assembly / positive regulation of diacylglycerol kinase activity / negative regulation of establishment of protein localization to mitochondrion / neurofibrillary tangle / positive regulation of protein localization to synapse / microtubule lateral binding / tubulin complex / phosphatidylinositol bisphosphate binding / main axon / regulation of long-term synaptic depression / negative regulation of kinase activity / negative regulation of tubulin deacetylation / generation of neurons / positive regulation of protein localization / regulation of chromosome organization / rRNA metabolic process / internal protein amino acid acetylation / regulation of mitochondrial fission / intracellular distribution of mitochondria / axonal transport of mitochondrion / axon development / central nervous system neuron development / regulation of microtubule polymerization / microtubule polymerization / minor groove of adenine-thymine-rich DNA binding / lipoprotein particle binding / dynactin binding / apolipoprotein binding / glial cell projection / negative regulation of mitochondrial membrane potential / protein polymerization / negative regulation of mitochondrial fission / axolemma / Caspase-mediated cleavage of cytoskeletal proteins / regulation of microtubule polymerization or depolymerization / positive regulation of axon extension / regulation of microtubule cytoskeleton organization / Activation of AMPK downstream of NMDARs / supramolecular fiber organization / regulation of cellular response to heat / stress granule assembly / cytoplasmic microtubule organization / regulation of calcium-mediated signaling / axon cytoplasm / positive regulation of microtubule polymerization / somatodendritic compartment / cellular response to brain-derived neurotrophic factor stimulus / synapse assembly / phosphatidylinositol binding / nuclear periphery / cellular response to nerve growth factor stimulus / positive regulation of superoxide anion generation / protein phosphatase 2A binding / regulation of autophagy / astrocyte activation / response to lead ion / synapse organization / microglial cell activation / Hsp90 protein binding / regulation of synaptic plasticity / PKR-mediated signaling / protein homooligomerization / memory / cytoplasmic ribonucleoprotein granule / SH3 domain binding / microtubule cytoskeleton organization / cellular response to reactive oxygen species / activation of cysteine-type endopeptidase activity involved in apoptotic process / neuron projection development / microtubule cytoskeleton / cell-cell signaling / protein-macromolecule adaptor activity / actin binding / cellular response to heat / single-stranded DNA binding / protein-folding chaperone binding / cell body / growth cone / microtubule binding / double-stranded DNA binding / microtubule / amyloid fibril formation / sequence-specific DNA binding / dendritic spine / learning or memory / nuclear speck / neuron projection / membrane raft / axon / negative regulation of gene expression / neuronal cell body / DNA damage response / dendrite / protein kinase binding / enzyme binding / mitochondrion / DNA binding Similarity search - Function | |||||||||||||||
Biological species | Homo sapiens (human) | |||||||||||||||
Method | helical reconstruction / cryo EM / Resolution: 3.0 Å | |||||||||||||||
Authors | Wilkinson MW / Gilbert MAG / Fatima N / Jenkins J / O'Sullivan TJ / Schertel A / Halfon Y / Morrema THJ / Geibel M / Ranson NA ...Wilkinson MW / Gilbert MAG / Fatima N / Jenkins J / O'Sullivan TJ / Schertel A / Halfon Y / Morrema THJ / Geibel M / Ranson NA / Radford SE / Hoozemans JJM / Frank RAW | |||||||||||||||
Funding support | United Kingdom, 4 items
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Citation | Journal: Nature / Year: 2024 Title: CryoET of β-amyloid and tau within postmortem Alzheimer's disease brain. Authors: Madeleine A G Gilbert / Nayab Fatima / Joshua Jenkins / Thomas J O'Sullivan / Andreas Schertel / Yehuda Halfon / Martin Wilkinson / Tjado H J Morrema / Mirjam Geibel / Randy J Read / Neil A ...Authors: Madeleine A G Gilbert / Nayab Fatima / Joshua Jenkins / Thomas J O'Sullivan / Andreas Schertel / Yehuda Halfon / Martin Wilkinson / Tjado H J Morrema / Mirjam Geibel / Randy J Read / Neil A Ranson / Sheena E Radford / Jeroen J M Hoozemans / René A W Frank / Abstract: A defining pathological feature of most neurodegenerative diseases is the assembly of proteins into amyloid that form disease-specific structures. In Alzheimer's disease, this is characterized by the ...A defining pathological feature of most neurodegenerative diseases is the assembly of proteins into amyloid that form disease-specific structures. In Alzheimer's disease, this is characterized by the deposition of β-amyloid and tau with disease-specific conformations. The in situ structure of amyloid in the human brain is unknown. Here, using cryo-fluorescence microscopy-targeted cryo-sectioning, cryo-focused ion beam-scanning electron microscopy lift-out and cryo-electron tomography, we determined in-tissue architectures of β-amyloid and tau pathology in a postmortem Alzheimer's disease donor brain. β-amyloid plaques contained a mixture of fibrils, some of which were branched, and protofilaments, arranged in parallel arrays and lattice-like structures. Extracellular vesicles and cuboidal particles defined the non-amyloid constituents of β-amyloid plaques. By contrast, tau inclusions formed parallel clusters of unbranched filaments. Subtomogram averaging a cluster of 136 tau filaments in a single tomogram revealed the polypeptide backbone conformation and filament polarity orientation of paired helical filaments within tissue. Filaments within most clusters were similar to each other, but were different between clusters, showing amyloid heterogeneity that is spatially organized by subcellular location. The in situ structural approaches outlined here for human donor tissues have applications to a broad range of neurodegenerative diseases. | |||||||||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_18990.map.gz | 38.9 MB | EMDB map data format | |
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Header (meta data) | emd-18990-v30.xml emd-18990.xml | 18.6 KB 18.6 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_18990_fsc.xml | 11.9 KB | Display | FSC data file |
Images | emd_18990.png | 93.5 KB | ||
Filedesc metadata | emd-18990.cif.gz | 5.9 KB | ||
Others | emd_18990_half_map_1.map.gz emd_18990_half_map_2.map.gz | 114 MB 114 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-18990 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-18990 | HTTPS FTP |
-Validation report
Summary document | emd_18990_validation.pdf.gz | 1000.7 KB | Display | EMDB validaton report |
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Full document | emd_18990_full_validation.pdf.gz | 1000.2 KB | Display | |
Data in XML | emd_18990_validation.xml.gz | 19.5 KB | Display | |
Data in CIF | emd_18990_validation.cif.gz | 25.7 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-18990 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-18990 | HTTPS FTP |
-Related structure data
Related structure data | C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_18990.map.gz / Format: CCP4 / Size: 144.7 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Annotation | Postprocessed sharpened map of tau PHF fibrils extracted from AD patient brain | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.83 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: halfmap1
File | emd_18990_half_map_1.map | ||||||||||||
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Annotation | halfmap1 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: halfmap2
File | emd_18990_half_map_2.map | ||||||||||||
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Annotation | halfmap2 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : tau PHF amyloid fibril
Entire | Name: tau PHF amyloid fibril |
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Components |
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-Supramolecule #1: tau PHF amyloid fibril
Supramolecule | Name: tau PHF amyloid fibril / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Homo sapiens (human) / Organ: Brain |
-Macromolecule #1: Microtubule-associated protein tau
Macromolecule | Name: Microtubule-associated protein tau / type: protein_or_peptide / ID: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) / Organ: Brain |
Sequence | String: MAEPRQEFEV MEDHAGTYGL GDRKDQGGYT MHQDQEGDTD AGLKESPLQT PTEDGSEEPG SETSDAKST PTAEDVTAPL VDEGAPGKQA AAQPHTEIPE GTTAEEAGIG DTPSLEDEAA G HVTQEPES GKVVQEGFLR EPGPPGLSHQ LMSGMPGAPL LPEGPREATR ...String: MAEPRQEFEV MEDHAGTYGL GDRKDQGGYT MHQDQEGDTD AGLKESPLQT PTEDGSEEPG SETSDAKST PTAEDVTAPL VDEGAPGKQA AAQPHTEIPE GTTAEEAGIG DTPSLEDEAA G HVTQEPES GKVVQEGFLR EPGPPGLSHQ LMSGMPGAPL LPEGPREATR QPSGTGPEDT EG GRHAPEL LKHQLLGDLH QEGPPLKGAG GKERPGSKEE VDEDRDVDES SPQDSPPSKA SPA QDGRPP QTAAREATSI PGFPAEGAIP LPVDFLSKVS TEIPASEPDG PSVGRAKGQD APLE FTFHV EITPNVQKEQ AHSEEHLGRA AFPGAPGEGP EARGPSLGED TKEADLPEPS EKQPA AAPR GKPVSRVPQL KARMVSKSKD GTGSDDKKAK TSTRSSAKTL KNRPCLSPKH PTPGSS DPL IQPSSPAVCP EPPSSPKYVS SVTSRTGSSG AKEMKLKGAD GKTKIATPRG AAPPGQK GQ ANATRIPAKT PPAPKTPPSS GEPPKSGDRS GYSSPGSPGT PGSRSRTPSL PTPPTREP K KVAVVRTPPK SPSSAKSRLQ TAPVPMPDLK NVKSKIGSTE NLKHQPGGGK VQIINKKLD LSNVQSKCGS KDNIKHVPGG GSVQIVYKPV DLSKVTSKCG SLGNIHHKPG GGQVEVKSEK LDFKDRVQS KIGSLDNITH VPGGGNKKIE THKLTFRENA KAKTDHGAEI VYKSPVVSGD T SPRHLSNV SSTGSIDMVD SPQLATLADE VSASLAKQGL UniProtKB: Microtubule-associated protein tau |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | helical reconstruction |
Aggregation state | filament |
-Sample preparation
Buffer | pH: 7.4 / Component:
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Grid | Model: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 300 / Pretreatment - Type: PLASMA CLEANING / Pretreatment - Time: 60 sec. | |||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 90 % / Chamber temperature: 279 K / Instrument: FEI VITROBOT MARK IV | |||||||||
Details | Frozen brain section was homogenised and purified using sarkosyl detergent. |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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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: 1 / Number real images: 10860 / Average exposure time: 4.0 sec. / Average electron dose: 44.0 e/Å2 Details: Each EER movie was fractionated and tif compressed into 38 frames with a dose of 1.16 e-/A2/frame prior to processing |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | C2 aperture diameter: 50.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 2.7 µm / Nominal defocus min: 1.5 µm / Nominal magnification: 96000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |