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Yorodumi- EMDB-17383: Tau filaments extracted from human brain with the DeltaK281 mutat... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-17383 | |||||||||
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Title | Tau filaments extracted from human brain with the DeltaK281 mutation in MAPT | |||||||||
Map data | ||||||||||
Sample |
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Keywords | DeltaK281 / Tau / Amyloid filament / Cross-beta-sheet / PROTEIN FIBRIL | |||||||||
Function / homology | Function and homology information plus-end-directed organelle transport along microtubule / histone-dependent DNA binding / neurofibrillary tangle assembly / positive regulation of diacylglycerol kinase activity / axonal transport / negative regulation of establishment of protein localization to mitochondrion / neurofibrillary tangle / positive regulation of protein localization to synapse / microtubule lateral binding / negative regulation of mitochondrial fission ...plus-end-directed organelle transport along microtubule / histone-dependent DNA binding / neurofibrillary tangle assembly / positive regulation of diacylglycerol kinase activity / axonal transport / negative regulation of establishment of protein localization to mitochondrion / neurofibrillary tangle / positive regulation of protein localization to synapse / microtubule lateral binding / negative regulation of mitochondrial fission / 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 / rRNA metabolic process / internal protein amino acid acetylation / regulation of chromosome organization / regulation of mitochondrial fission / axonal transport of mitochondrion / intracellular distribution of mitochondria / 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 / glial cell projection / apolipoprotein binding / negative regulation of mitochondrial membrane potential / protein polymerization / 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 / cytoplasmic microtubule organization / supramolecular fiber organization / regulation of cellular response to heat / stress granule assembly / positive regulation of superoxide anion generation / regulation of calcium-mediated signaling / axon cytoplasm / positive regulation of microtubule polymerization / somatodendritic compartment / synapse assembly / cellular response to brain-derived neurotrophic factor stimulus / astrocyte activation / phosphatidylinositol binding / nuclear periphery / cellular response to nerve growth factor stimulus / protein phosphatase 2A binding / regulation of autophagy / response to lead ion / synapse organization / microglial cell activation / cellular response to reactive oxygen species / Hsp90 protein binding / PKR-mediated signaling / protein homooligomerization / regulation of synaptic plasticity / memory / activation of cysteine-type endopeptidase activity involved in apoptotic process / microtubule cytoskeleton organization / SH3 domain binding / cytoplasmic ribonucleoprotein granule / microtubule cytoskeleton / neuron projection development / cell-cell signaling / double-stranded DNA binding / protein-macromolecule adaptor activity / single-stranded DNA binding / actin binding / protein-folding chaperone binding / cellular response to heat / cell body / growth cone / microtubule binding / sequence-specific DNA binding / amyloid fibril formation / microtubule / learning or memory / dendritic spine / 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: 2.61 Å | |||||||||
Authors | Schweighauser M / Garringer HJ / Klingstedt T / Masuda-Suzukake M / Murrell JR / Vidal R / Scheres SHW / Goedert M / Ghetti B / Newell KL | |||||||||
Funding support | United Kingdom, 1 items
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Citation | Journal: Acta Neuropathol / Year: 2023 Title: Mutation ∆K281 in MAPT causes Pick's disease. Authors: Manuel Schweighauser / Holly J Garringer / Therése Klingstedt / K Peter R Nilsson / Masami Masuda-Suzukake / Jill R Murrell / Shannon L Risacher / Ruben Vidal / Sjors H W Scheres / Michel ...Authors: Manuel Schweighauser / Holly J Garringer / Therése Klingstedt / K Peter R Nilsson / Masami Masuda-Suzukake / Jill R Murrell / Shannon L Risacher / Ruben Vidal / Sjors H W Scheres / Michel Goedert / Bernardino Ghetti / Kathy L Newell / Abstract: Two siblings with deletion mutation ∆K281 in MAPT developed frontotemporal dementia. At autopsy, numerous inclusions of hyperphosphorylated 3R Tau were present in neurons and glial cells of ...Two siblings with deletion mutation ∆K281 in MAPT developed frontotemporal dementia. At autopsy, numerous inclusions of hyperphosphorylated 3R Tau were present in neurons and glial cells of neocortex and some subcortical regions, including hippocampus, caudate/putamen and globus pallidus. The inclusions were argyrophilic with Bodian silver, but not with Gallyas-Braak silver. They were not labelled by an antibody specific for tau phosphorylated at S262 and/or S356. The inclusions were stained by luminescent conjugated oligothiophene HS-84, but not by bTVBT4. Electron cryo-microscopy revealed that the core of tau filaments was made of residues K254-F378 of 3R Tau and was indistinguishable from that of Pick's disease. We conclude that MAPT mutation ∆K281 causes Pick's disease. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_17383.map.gz | 39.1 MB | EMDB map data format | |
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Header (meta data) | emd-17383-v30.xml emd-17383.xml | 16 KB 16 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_17383_fsc.xml | 13.8 KB | Display | FSC data file |
Images | emd_17383.png | 38 KB | ||
Masks | emd_17383_msk_1.map | 226.3 MB | Mask map | |
Filedesc metadata | emd-17383.cif.gz | 5.4 KB | ||
Others | emd_17383_half_map_1.map.gz emd_17383_half_map_2.map.gz | 180 MB 180 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-17383 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-17383 | HTTPS FTP |
-Validation report
Summary document | emd_17383_validation.pdf.gz | 804.2 KB | Display | EMDB validaton report |
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Full document | emd_17383_full_validation.pdf.gz | 803.8 KB | Display | |
Data in XML | emd_17383_validation.xml.gz | 21.6 KB | Display | |
Data in CIF | emd_17383_validation.cif.gz | 28.2 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-17383 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-17383 | HTTPS FTP |
-Related structure data
Related structure data | 8p34MC M: atomic model generated by this map 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_17383.map.gz / Format: CCP4 / Size: 226.3 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Voxel size | X=Y=Z: 0.93 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
File | emd_17383_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_17383_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_17383_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Tau filaments extracted from human brain with DeltaK281 mutation
Entire | Name: Tau filaments extracted from human brain with DeltaK281 mutation |
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Components |
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-Supramolecule #1: Tau filaments extracted from human brain with DeltaK281 mutation
Supramolecule | Name: Tau filaments extracted from human brain with DeltaK281 mutation type: tissue / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Homo sapiens (human) / Organ: Brain / Tissue: Frontal cortex grey matter |
-Macromolecule #1: Microtubule-associated protein tau
Macromolecule | Name: Microtubule-associated protein tau / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 10.135665 KDa |
Sequence | String: KNVKSKIGST ENLKHQPGGG KVQIVYKPVD LSKVTSKCGS LGNIHHKPGG GQVEVKSEKL DFKDRVQSKI GSLDNITHVP GGGNKKIET HKLTF 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 / Details: 20 mM Tris-HCL, 100 mM NaCl |
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Grid | Model: Quantifoil R1.2/1.3 / Material: GOLD / Mesh: 300 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 60 sec. |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277.15 K / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Specialist optics | Phase plate: OTHER |
Image recording | Film or detector model: GATAN K3 (6k x 4k) / Number real images: 41385 / Average exposure time: 1.0 sec. / Average electron dose: 37.7 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.8000000000000003 µm / Nominal defocus min: 1.8 µm |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |