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Yorodumi- EMDB-16329: Chronic traumatic encephalopathy tau filaments with PET ligand fl... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-16329 | |||||||||||||||||||||
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Title | Chronic traumatic encephalopathy tau filaments with PET ligand flortaucipir | |||||||||||||||||||||
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Sample |
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Keywords | Chronic traumatic encephalopathy / Primary age-related tauopathy / Tau filaments / PET ligand / Flortaucipir / 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: 2.6 Å | |||||||||||||||||||||
Authors | Shi Y / Ghetti B / Goedert M / Scheres SHW | |||||||||||||||||||||
Funding support | United Kingdom, Switzerland, United States, 6 items
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Citation | Journal: J Mol Biol / Year: 2023 Title: Cryo-EM Structures of Chronic Traumatic Encephalopathy Tau Filaments with PET Ligand Flortaucipir. Authors: Yang Shi / Bernardino Ghetti / Michel Goedert / Sjors H W Scheres / Abstract: Positron emission tomography (PET) imaging allows monitoring the progression of amyloid aggregation in the living brain. [F]-Flortaucipir is the only approved PET tracer compound for the ...Positron emission tomography (PET) imaging allows monitoring the progression of amyloid aggregation in the living brain. [F]-Flortaucipir is the only approved PET tracer compound for the visualisation of tau aggregation. Here, we describe cryo-EM experiments on tau filaments in the presence and absence of flortaucipir. We used tau filaments isolated from the brain of an individual with Alzheimer's disease (AD), and from the brain of an individual with primary age-related tauopathy (PART) with a co-pathology of chronic traumatic encephalopathy (CTE). Unexpectedly, we were unable to visualise additional cryo-EM density for flortaucipir for AD paired helical or straight filaments (PHFs or SFs), but we did observe density for flortaucipir binding to CTE Type I filaments from the case with PART. In the latter, flortaucipir binds in a 1:1 molecular stoichiometry with tau, adjacent to lysine 353 and aspartate 358. By adopting a tilted geometry with respect to the helical axis, the 4.7 Å distance between neighbouring tau monomers is reconciled with the 3.5 Å distance consistent with π-π-stacking between neighbouring molecules of flortaucipir. | |||||||||||||||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_16329.map.gz | 41.3 MB | EMDB map data format | |
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Header (meta data) | emd-16329-v30.xml emd-16329.xml | 15.2 KB 15.2 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_16329_fsc.xml | 10.7 KB | Display | FSC data file |
Images | emd_16329.png | 82.1 KB | ||
Masks | emd_16329_msk_1.map | 103 MB | Mask map | |
Filedesc metadata | emd-16329.cif.gz | 5.4 KB | ||
Others | emd_16329_half_map_1.map.gz emd_16329_half_map_2.map.gz | 80.8 MB 80.8 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-16329 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-16329 | HTTPS FTP |
-Validation report
Summary document | emd_16329_validation.pdf.gz | 1 MB | Display | EMDB validaton report |
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Full document | emd_16329_full_validation.pdf.gz | 1 MB | Display | |
Data in XML | emd_16329_validation.xml.gz | 18 KB | Display | |
Data in CIF | emd_16329_validation.cif.gz | 23.2 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-16329 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-16329 | HTTPS FTP |
-Related structure data
Related structure data | 8bynMC 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_16329.map.gz / Format: CCP4 / Size: 103 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Voxel size | X=Y=Z: 0.824 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
File | emd_16329_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_16329_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_16329_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Sarkosyl-insoluble fraction from the hippocampus of an individual...
Entire | Name: Sarkosyl-insoluble fraction from the hippocampus of an individual with primary age-related tauopathy |
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Components |
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-Supramolecule #1: Sarkosyl-insoluble fraction from the hippocampus of an individual...
Supramolecule | Name: Sarkosyl-insoluble fraction from the hippocampus of an individual with primary age-related tauopathy type: tissue / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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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 |
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 |
-Macromolecule #2: 7-(6-fluoranylpyridin-3-yl)-5~{H}-pyrido[4,3-b]indole
Macromolecule | Name: 7-(6-fluoranylpyridin-3-yl)-5~{H}-pyrido[4,3-b]indole / type: ligand / ID: 2 / Number of copies: 6 / Formula: S9C |
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Molecular weight | Theoretical: 263.269 Da |
Chemical component information | ChemComp-S9C: |
-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: 2.0 µm / Nominal defocus min: 1.0 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |