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Yorodumi- EMDB-28721: CryoEM structure of synthetic tau repeat R1R2 with two acetylated... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-28721 | ||||||||||||
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Title | CryoEM structure of synthetic tau repeat R1R2 with two acetylated lysines at positions 274 and 280 | ||||||||||||
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Sample |
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Keywords | Amyloid motif / acetylation / tau / repeat domain / post-translational modification / 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: 3.88 Å | ||||||||||||
Authors | Li L / Nguyen B / Mullapudi V / Saelices L / Joachimiak L | ||||||||||||
Funding support | United States, 3 items
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Citation | Journal: Structure / Year: 2023 Title: Disease-associated patterns of acetylation stabilize tau fibril formation. Authors: Li Li / Binh A Nguyen / Vishruth Mullapudi / Yang Li / Lorena Saelices / Lukasz A Joachimiak / Abstract: Assembly of tau into beta-sheet-rich amyloids dictates the pathology of a diversity of diseases. Lysine acetylation has been proposed to drive tau amyloid assembly, but no direct mechanism has ...Assembly of tau into beta-sheet-rich amyloids dictates the pathology of a diversity of diseases. Lysine acetylation has been proposed to drive tau amyloid assembly, but no direct mechanism has emerged. Using tau fragments, we identify patterns of acetylation that flank amyloidogenic motifs on the tau fragments that promote rapid fibril assembly. We determined a 3.9 Å cryo-EM amyloid fibril structure assembled from an acetylated tau fragment uncovering how lysine acetylation can mediate gain-of-function interactions. Comparison of the structure to an ex vivo tauopathy fibril reveals regions of structural similarity. Finally, we show that fibrils encoding disease-associated patterns of acetylation are active in cell-based tau aggregation assays. Our data uncover the dual role of lysine residues in limiting tau aggregation while their acetylation leads to stabilizing pro-aggregation interactions. Design of tau sequence with specific acetylation patterns may lead to controllable tau aggregation to direct folding of tau into distinct amyloid folds. | ||||||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_28721.map.gz | 2.3 MB | EMDB map data format | |
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Header (meta data) | emd-28721-v30.xml emd-28721.xml | 17.9 KB 17.9 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_28721_fsc.xml | 6.4 KB | Display | FSC data file |
Images | emd_28721.png | 60 KB | ||
Masks | emd_28721_msk_1.map | 22.2 MB | Mask map | |
Filedesc metadata | emd-28721.cif.gz | 4.7 KB | ||
Others | emd_28721_additional_1.map.gz emd_28721_half_map_1.map.gz emd_28721_half_map_2.map.gz | 16.8 MB 16.9 MB 16.9 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-28721 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-28721 | HTTPS FTP |
-Validation report
Summary document | emd_28721_validation.pdf.gz | 736.6 KB | Display | EMDB validaton report |
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Full document | emd_28721_full_validation.pdf.gz | 736.2 KB | Display | |
Data in XML | emd_28721_validation.xml.gz | 11.9 KB | Display | |
Data in CIF | emd_28721_validation.cif.gz | 16.1 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-28721 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-28721 | HTTPS FTP |
-Related structure data
Related structure data | 8fnzMC 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_28721.map.gz / Format: CCP4 / Size: 22.2 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: 1.66 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
File | emd_28721_msk_1.map | ||||||||||||
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Density Histograms |
-Additional map: #1
File | emd_28721_additional_1.map | ||||||||||||
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Density Histograms |
-Half map: #1
File | emd_28721_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_28721_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Acetylated tau repeat 1 and 2 fragment (AcR1R2)
Entire | Name: Acetylated tau repeat 1 and 2 fragment (AcR1R2) |
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Components |
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-Supramolecule #1: Acetylated tau repeat 1 and 2 fragment (AcR1R2)
Supramolecule | Name: Acetylated tau repeat 1 and 2 fragment (AcR1R2) / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all Details: Synthetic tau repeat R1R2 with two acetylated lysines at position 274 and 280 |
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Source (natural) | Organism: Homo sapiens (human) / Synthetically produced: Yes |
-Macromolecule #1: Acetylated tau repeat 1 and 2 fragment (AcR1R2)
Macromolecule | Name: Acetylated tau repeat 1 and 2 fragment (AcR1R2) / type: protein_or_peptide / ID: 1 / Details: (ALY): Acetylated lysine / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Sequence | String: TENLKHQPGG G(ALY)VQIIN(ALY) |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | helical reconstruction |
Aggregation state | filament |
-Sample preparation
Buffer | pH: 7.4 / Details: PBS |
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Grid | Model: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 300 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 30 sec. / Pretreatment - Atmosphere: OTHER |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 295 K / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Number grids imaged: 1 / Number real images: 5901 / Average exposure time: 4.5 sec. / Average electron dose: 52.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 2.4 µm / Nominal defocus min: 1.2 µm / Nominal magnification: 105000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |