+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-45589 | |||||||||
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Title | Alzheimer's Disease Seeded Mixed 0N4R and 0N3R Tau Fibrils | |||||||||
Map data | ||||||||||
Sample |
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Keywords | Tau / Amyloid / Cross-beta / Seeded-Fibril / 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 / tubulin complex ...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 / 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 / rRNA metabolic process / internal protein amino acid acetylation / regulation of chromosome organization / regulation of mitochondrial fission / axonal transport of mitochondrion / axon development / intracellular distribution of mitochondria / central nervous system neuron development / regulation of microtubule polymerization / microtubule polymerization / lipoprotein particle binding / minor groove of adenine-thymine-rich DNA binding / dynactin binding / glial cell projection / negative regulation of mitochondrial membrane potential / apolipoprotein binding / protein polymerization / axolemma / negative regulation of mitochondrial fission / 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 / positive regulation of protein localization / regulation of cellular response to heat / cytoplasmic microtubule organization / stress granule assembly / supramolecular fiber organization / regulation of calcium-mediated signaling / axon cytoplasm / somatodendritic compartment / positive regulation of microtubule polymerization / 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 / microglial cell activation / synapse organization / Hsp90 protein binding / protein homooligomerization / PKR-mediated signaling / regulation of synaptic plasticity / memory / activation of cysteine-type endopeptidase activity involved in apoptotic process / microtubule cytoskeleton organization / SH3 domain binding / cellular response to reactive oxygen species / cytoplasmic ribonucleoprotein granule / microtubule cytoskeleton / neuron projection development / cell-cell signaling / protein-macromolecule adaptor activity / protein-folding chaperone binding / single-stranded DNA binding / actin binding / cellular response to heat / cell body / growth cone / microtubule binding / double-stranded DNA binding / microtubule / sequence-specific DNA binding / amyloid fibril formation / dendritic spine / learning or memory / nuclear speck / neuron projection / membrane raft / axon / negative regulation of gene expression / neuronal cell body / dendrite / DNA damage response / protein kinase binding / enzyme binding / mitochondrion / DNA binding Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | helical reconstruction / cryo EM / Resolution: 2.69 Å | |||||||||
Authors | Duan P / Dregni AJ / Xu H / Changolkar L / Lee VM-Y / Hong M | |||||||||
Funding support | United States, 1 items
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Citation | Journal: J Biol Chem / Year: 2024 Title: Alzheimer's disease seeded tau forms paired helical filaments yet lacks seeding potential. Authors: Pu Duan / Aurelio J Dregni / Hong Xu / Lakshmi Changolkar / Virginia M-Y Lee / Edward B Lee / Mei Hong / Abstract: Alzheimer's disease (AD) and many other neurodegenerative diseases are characterized by pathological aggregation of the protein tau. These tau aggregates spread in a stereotypical spatiotemporal ...Alzheimer's disease (AD) and many other neurodegenerative diseases are characterized by pathological aggregation of the protein tau. These tau aggregates spread in a stereotypical spatiotemporal pattern in the brain of each disease, suggesting that the misfolded tau can recruit soluble monomers to adopt the same pathological structure. To investigate whether recruited tau indeed adopts the same structure and properties as the original seed, here we template recombinant full-length 0N3R tau, 0N4R tau, and an equimolar mixture of the two using sarkosyl-insoluble tau extracted from AD brain and determine the structures of the resulting fibrils using cryoelectron microscopy. We show that these cell-free amplified tau fibrils adopt the same molecular structure as the AD paired-helical filament (PHF) tau but are unable to template additional monomers. Therefore, the PHF structure alone is insufficient for defining the pathological properties of AD tau, and other biochemical components such as tau posttranslational modifications, other proteins, polyanionic cofactors, and salt are required for the prion-like serial propagation of tauopathies. | |||||||||
History |
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-Structure visualization
-Downloads & links
-EMDB archive
Map data | emd_45589.map.gz | 10.8 MB | EMDB map data format | |
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Header (meta data) | emd-45589-v30.xml emd-45589.xml | 17.7 KB 17.7 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_45589_fsc.xml | 13.5 KB | Display | FSC data file |
Images | emd_45589.png | 85.4 KB | ||
Masks | emd_45589_msk_1.map | 216 MB | Mask map | |
Filedesc metadata | emd-45589.cif.gz | 5.6 KB | ||
Others | emd_45589_additional_1.map.gz emd_45589_half_map_1.map.gz emd_45589_half_map_2.map.gz | 198.6 MB 171 MB 171 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-45589 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-45589 | HTTPS FTP |
-Validation report
Summary document | emd_45589_validation.pdf.gz | 772 KB | Display | EMDB validaton report |
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Full document | emd_45589_full_validation.pdf.gz | 771.6 KB | Display | |
Data in XML | emd_45589_validation.xml.gz | 21.4 KB | Display | |
Data in CIF | emd_45589_validation.cif.gz | 28.3 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-45589 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-45589 | HTTPS FTP |
-Related structure data
Related structure data | 9cgzMC 9cgxC 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_45589.map.gz / Format: CCP4 / Size: 216 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.06 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
File | emd_45589_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Amyloid Fibril of Mixed 0N4R and 0N3R Tau Seeded with Alzheimer's...
Entire | Name: Amyloid Fibril of Mixed 0N4R and 0N3R Tau Seeded with Alzheimer's Disease Tau from Human Brain |
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Components |
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-Supramolecule #1: Amyloid Fibril of Mixed 0N4R and 0N3R Tau Seeded with Alzheimer's...
Supramolecule | Name: Amyloid Fibril of Mixed 0N4R and 0N3R Tau Seeded with Alzheimer's Disease Tau from Human Brain type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: Isoform Fetal-tau of Microtubule-associated protein tau
Macromolecule | Name: Isoform Fetal-tau of Microtubule-associated protein tau type: protein_or_peptide / ID: 1 Details: Mixture of 0N4R and 0N3R monomers templated by Alzheimer's Disease Seeds Number of copies: 6 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 36.821121 KDa |
Recombinant expression | Organism: Escherichia coli (E. coli) |
Sequence | String: MAEPRQEFEV MEDHAGTYGL GDRKDQGGYT MHQDQEGDTD AGLKAEEAGI GDTPSLEDEA AGHVTQARMV SKSKDGTGSD DKKAKGADG KTKIATPRGA APPGQKGQAN ATRIPAKTPP APKTPPSSGE PPKSGDRSGY SSPGSPGTPG SRSRTPSLPT P PTREPKKV ...String: MAEPRQEFEV MEDHAGTYGL GDRKDQGGYT MHQDQEGDTD AGLKAEEAGI GDTPSLEDEA AGHVTQARMV SKSKDGTGSD DKKAKGADG KTKIATPRGA APPGQKGQAN ATRIPAKTPP APKTPPSSGE PPKSGDRSGY SSPGSPGTPG SRSRTPSLPT P PTREPKKV AVVRTPPKSP SSAKSRLQTA PVPMPDLKNV KSKIGSTENL KHQPGGGKVQ IVYKPVDLSK VTSKCGSLGN IH HKPGGGQ VEVKSEKLDF KDRVQSKIGS LDNITHVPGG GNKKIETHKL TFRENAKAKT DHGAEIVYKS PVVSGDTSPR HLS NVSSTG 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
Concentration | 1.6 mg/mL |
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Buffer | pH: 7.4 |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK I |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Number grids imaged: 1 / Number real images: 7917 / Average exposure time: 2.25 sec. / Average electron dose: 45.7 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | C2 aperture diameter: 100.0 µm / Illumination mode: SPOT SCAN / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 2.0 µm / Nominal defocus min: 0.2 µm / Nominal magnification: 81000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |