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Yorodumi- EMDB-14316: In vitro assembled 266/297 - 391 tau filaments with NaHCO3 and Na... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-14316 | |||||||||
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Title | In vitro assembled 266/297 - 391 tau filaments with NaHCO3 and NaCl (16a) | |||||||||
Map data | Sharpened map of in vitro assembled 266/297 - 391 tau filaments with NaHCO3 and NaCl (16a) | |||||||||
Sample |
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Keywords | Alzheimer's Disease / Amyloid / Tau / Neurodegeneration / 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: 2.75 Å | |||||||||
Authors | Lovestam S / Scheres SHW | |||||||||
Funding support | United Kingdom, 1 items
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Citation | Journal: Elife / Year: 2022 Title: Assembly of recombinant tau into filaments identical to those of Alzheimer's disease and chronic traumatic encephalopathy. Authors: Sofia Lövestam / Fujiet Adrian Koh / Bart van Knippenberg / Abhay Kotecha / Alexey G Murzin / Michel Goedert / Sjors H W Scheres / Abstract: Abundant filamentous inclusions of tau are characteristic of more than 20 neurodegenerative diseases that are collectively termed tauopathies. Electron cryo-microscopy (cryo-EM) structures of tau ...Abundant filamentous inclusions of tau are characteristic of more than 20 neurodegenerative diseases that are collectively termed tauopathies. Electron cryo-microscopy (cryo-EM) structures of tau amyloid filaments from human brain revealed that distinct tau folds characterise many different diseases. A lack of laboratory-based model systems to generate these structures has hampered efforts to uncover the molecular mechanisms that underlie tauopathies. Here, we report in vitro assembly conditions with recombinant tau that replicate the structures of filaments from both Alzheimer's disease (AD) and chronic traumatic encephalopathy (CTE), as determined by cryo-EM. Our results suggest that post-translational modifications of tau modulate filament assembly, and that previously observed additional densities in AD and CTE filaments may arise from the presence of inorganic salts, like phosphates and sodium chloride. In vitro assembly of tau into disease-relevant filaments will facilitate studies to determine their roles in different diseases, as well as the development of compounds that specifically bind to these structures or prevent their formation. | |||||||||
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_14316.map.gz | 46.9 MB | EMDB map data format | |
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Header (meta data) | emd-14316-v30.xml emd-14316.xml | 16.5 KB 16.5 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_14316_fsc.xml | 13.6 KB | Display | FSC data file |
Images | emd_14316.png | 29.1 KB | ||
Filedesc metadata | emd-14316.cif.gz | 5.4 KB | ||
Others | emd_14316_additional_1.map.gz emd_14316_half_map_1.map.gz emd_14316_half_map_2.map.gz | 202.1 MB 171.1 MB 171.1 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-14316 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-14316 | HTTPS FTP |
-Validation report
Summary document | emd_14316_validation.pdf.gz | 1017.8 KB | Display | EMDB validaton report |
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Full document | emd_14316_full_validation.pdf.gz | 1017.4 KB | Display | |
Data in XML | emd_14316_validation.xml.gz | 21.3 KB | Display | |
Data in CIF | emd_14316_validation.cif.gz | 27.9 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-14316 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-14316 | HTTPS FTP |
-Related structure data
Related structure data | 7r4tMC 7qjvC 7qjwC 7qjxC 7qjyC 7qjzC 7qk1C 7qk2C 7qk3C 7qk5C 7qk6C 7qkfC 7qkgC 7qkhC 7qkiC 7qkjC 7qkkC 7qklC 7qkmC 7qkuC 7qkvC 7qkwC 7qkxC 7qkyC 7qkzC 7ql0C 7ql1C 7ql2C 7ql3C 7ql4C 7r5hC M: atomic model generated by this map C: citing same article (ref.) |
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Similar 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_14316.map.gz / Format: CCP4 / Size: 216 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Sharpened map of in vitro assembled 266/297 - 391 tau filaments with NaHCO3 and NaCl (16a) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.824 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Additional map: Unsharpened map of in vitro assembled 266/297 -...
File | emd_14316_additional_1.map | ||||||||||||
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Annotation | Unsharpened map of in vitro assembled 266/297 - 391 tau filaments with NaHCO3 and NaCl (16a) | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half map 1 of in vitro assembled 266/297...
File | emd_14316_half_map_1.map | ||||||||||||
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Annotation | Half map 1 of in vitro assembled 266/297 - 391 tau filaments with NaHCO3 and NaCl (16a) | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half map 2 of in vitro assembled 266/297...
File | emd_14316_half_map_2.map | ||||||||||||
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Annotation | Half map 2 of in vitro assembled 266/297 - 391 tau filaments with NaHCO3 and NaCl (16a) | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Tau
Entire | Name: Tau |
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Components |
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-Supramolecule #1: Tau
Supramolecule | Name: Tau / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: Microtubule-associated protein tau
Macromolecule | Name: Microtubule-associated protein tau / type: protein_or_peptide / ID: 1 / Number of copies: 6 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 45.919871 KDa |
Recombinant expression | Organism: Escherichia coli (E. coli) |
Sequence | String: MAEPRQEFEV MEDHAGTYGL GDRKDQGGYT MHQDQEGDTD AGLKESPLQT PTEDGSEEPG SETSDAKSTP TAEDVTAPLV DEGAPGKQA AAQPHTEIPE GTTAEEAGIG DTPSLEDEAA GHVTQARMVS KSKDGTGSDD KKAKGADGKT KIATPRGAAP P GQKGQANA ...String: MAEPRQEFEV MEDHAGTYGL GDRKDQGGYT MHQDQEGDTD AGLKESPLQT PTEDGSEEPG SETSDAKSTP TAEDVTAPLV DEGAPGKQA AAQPHTEIPE GTTAEEAGIG DTPSLEDEAA GHVTQARMVS KSKDGTGSDD KKAKGADGKT KIATPRGAAP P GQKGQANA TRIPAKTPPA PKTPPSSGEP PKSGDRSGYS SPGSPGTPGS RSRTPSLPTP PTREPKKVAV VRTPPKSPSS AK SRLQTAP VPMPDLKNVK SKIGSTENLK HQPGGGKVQI INKKLDLSNV QSKCGSKDNI KHVPGGGSVQ IVYKPVDLSK VTS KCGSLG NIHHKPGGGQ VEVKSEKLDF KDRVQSKIGS LDNITHVPGG GNKKIETHKL TFRENAKAKT DHGAEIVYKS PVVS GDTSP RHLSNVSSTG SIDMVDSPQL ATLADEVSAS LAKQGL 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 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 40.0 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: 3.5 µm / Nominal defocus min: 1.0 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
-Atomic model buiding 1
Refinement | Protocol: AB INITIO MODEL |
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Output model | PDB-7r4t: |