+Open data
-Basic information
Entry | Database: PDB / ID: 8oth | |||||||||
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Title | TypeII tau filament from Kii ALS/PDC | |||||||||
Components | Microtubule-associated protein tau | |||||||||
Keywords | PROTEIN FIBRIL / TypeII tau filaments / Kii ALS/PDC | |||||||||
Function / homology | Function and homology information plus-end-directed organelle transport along microtubule / histone-dependent DNA binding / neurofibrillary tangle assembly / : / negative regulation of establishment of protein localization to mitochondrion / neurofibrillary tangle / positive regulation of protein localization to synapse / microtubule lateral binding / axonal transport / main axon ...plus-end-directed organelle transport along microtubule / histone-dependent DNA binding / neurofibrillary tangle assembly / : / negative regulation of establishment of protein localization to mitochondrion / neurofibrillary tangle / positive regulation of protein localization to synapse / microtubule lateral binding / axonal transport / main axon / tubulin complex / regulation of long-term synaptic depression / phosphatidylinositol bisphosphate binding / negative regulation of tubulin deacetylation / negative regulation of kinase activity / generation of neurons / internal protein amino acid acetylation / regulation of chromosome organization / rRNA metabolic process / axonal transport of mitochondrion / regulation of mitochondrial fission / axon development / intracellular distribution of mitochondria / central nervous system neuron development / regulation of microtubule polymerization / microtubule polymerization / minor groove of adenine-thymine-rich DNA binding / lipoprotein particle binding / dynactin binding / negative regulation of mitochondrial membrane potential / glial cell projection / apolipoprotein binding / protein polymerization / negative regulation of mitochondrial fission / axolemma / regulation of microtubule polymerization or depolymerization / positive regulation of axon extension / Caspase-mediated cleavage of cytoskeletal proteins / regulation of microtubule cytoskeleton organization / synapse assembly / cytoplasmic microtubule organization / Activation of AMPK downstream of NMDARs / regulation of cellular response to heat / positive regulation of protein localization / supramolecular fiber organization / regulation of calcium-mediated signaling / axon cytoplasm / stress granule assembly / somatodendritic compartment / cellular response to brain-derived neurotrophic factor stimulus / positive regulation of microtubule polymerization / phosphatidylinositol binding / nuclear periphery / positive regulation of superoxide anion generation / protein phosphatase 2A binding / regulation of autophagy / astrocyte activation / cellular response to reactive oxygen species / response to lead ion / Hsp90 protein binding / microglial cell activation / synapse organization / cellular response to nerve growth factor stimulus / : / protein homooligomerization / regulation of synaptic plasticity / PKR-mediated signaling / memory / microtubule cytoskeleton organization / SH3 domain binding / cytoplasmic ribonucleoprotein granule / neuron projection development / microtubule cytoskeleton / cell-cell signaling / single-stranded DNA binding / actin binding / protein-folding chaperone binding / cellular response to heat / protein-macromolecule adaptor activity / cell body / growth cone / double-stranded DNA binding / microtubule binding / sequence-specific DNA binding / microtubule / dendritic spine / amyloid fibril formation / 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 | ELECTRON MICROSCOPY / helical reconstruction / cryo EM / Resolution: 3.4 Å | |||||||||
Authors | Qi, C. / Yang, S. / Scheres, S.H.W. / Goedert, M. | |||||||||
Funding support | United Kingdom, 2items
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Citation | Journal: Proc Natl Acad Sci U S A / Year: 2023 Title: Tau filaments from amyotrophic lateral sclerosis/parkinsonism-dementia complex adopt the CTE fold. Authors: Chao Qi / Bert M Verheijen / Yasumasa Kokubo / Yang Shi / Stephan Tetter / Alexey G Murzin / Asa Nakahara / Satoru Morimoto / Marc Vermulst / Ryogen Sasaki / Eleonora Aronica / Yoshifumi ...Authors: Chao Qi / Bert M Verheijen / Yasumasa Kokubo / Yang Shi / Stephan Tetter / Alexey G Murzin / Asa Nakahara / Satoru Morimoto / Marc Vermulst / Ryogen Sasaki / Eleonora Aronica / Yoshifumi Hirokawa / Kiyomitsu Oyanagi / Akiyoshi Kakita / Benjamin Ryskeldi-Falcon / Mari Yoshida / Masato Hasegawa / Sjors H W Scheres / Michel Goedert / Abstract: The amyotrophic lateral sclerosis/parkinsonism-dementia complex (ALS/PDC) of the island of Guam and the Kii peninsula of Japan is a fatal neurodegenerative disease of unknown cause that is ...The amyotrophic lateral sclerosis/parkinsonism-dementia complex (ALS/PDC) of the island of Guam and the Kii peninsula of Japan is a fatal neurodegenerative disease of unknown cause that is characterized by the presence of abundant filamentous tau inclusions in brains and spinal cords. Here, we used electron cryo-microscopy to determine the structures of tau filaments from the cerebral cortex of three cases of ALS/PDC from Guam and eight cases from Kii, as well as from the spinal cord of two of the Guam cases. Tau filaments had the chronic traumatic encephalopathy (CTE) fold, with variable amounts of Type I and Type II filaments. Paired helical tau filaments were also found in three Kii cases and tau filaments with the corticobasal degeneration fold in one Kii case. We identified a new Type III CTE tau filament, where protofilaments pack against each other in an antiparallel fashion. ALS/PDC is the third known tauopathy with CTE-type filaments and abundant tau inclusions in cortical layers II/III, the others being CTE and subacute sclerosing panencephalitis. Because these tauopathies are believed to have environmental causes, our findings support the hypothesis that ALS/PDC is caused by exogenous factors. | |||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8oth.cif.gz | 105.1 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8oth.ent.gz | 68.9 KB | Display | PDB format |
PDBx/mmJSON format | 8oth.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8oth_validation.pdf.gz | 1.3 MB | Display | wwPDB validaton report |
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Full document | 8oth_full_validation.pdf.gz | 1.3 MB | Display | |
Data in XML | 8oth_validation.xml.gz | 30.8 KB | Display | |
Data in CIF | 8oth_validation.cif.gz | 42.4 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ot/8oth ftp://data.pdbj.org/pub/pdb/validation_reports/ot/8oth | HTTPS FTP |
-Related structure data
Related structure data | 17179MC 8ot6C 8ot9C 8otcC 8otdC 8oteC 8otfC 8otgC 8otiC 8otjC C: citing same article (ref.) M: map data used to model this data |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 45919.871 Da / Num. of mol.: 5 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P10636 |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: FILAMENT / 3D reconstruction method: helical reconstruction |
-Sample preparation
Component | Name: TypeII tau filaments from Kii ALS/PDC / Type: COMPLEX / Entity ID: all / Source: NATURAL |
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Source (natural) | Organism: Homo sapiens (human) |
Buffer solution | pH: 7.4 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2000 nm / Nominal defocus min: 1000 nm |
Image recording | Electron dose: 40 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
Image processing | Details: TypeII tau filament from Kii ALS/PDC |
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CTF correction | Type: NONE |
Helical symmerty | Angular rotation/subunit: 179.36 ° / Axial rise/subunit: 2.39 Å / Axial symmetry: C1 |
3D reconstruction | Resolution: 3.4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 33337 / Symmetry type: HELICAL |