+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-18354 | |||||||||
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Title | CTE Tau intermediate amyloid (MIA-2) | |||||||||
Map data | Sharpened map | |||||||||
Sample |
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Keywords | Amyloid / tau / PROTEIN FIBRIL | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | helical reconstruction / cryo EM / Resolution: 4.22 Å | |||||||||
Authors | Lovestam S / Li D / Scheres SHW / Goedert M | |||||||||
Funding support | United Kingdom, 1 items
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Citation | Journal: Nature / Year: 2024 Title: Disease-specific tau filaments assemble via polymorphic intermediates. Authors: Sofia Lövestam / David Li / Jane L Wagstaff / Abhay Kotecha / Dari Kimanius / Stephen H McLaughlin / Alexey G Murzin / Stefan M V Freund / Michel Goedert / Sjors H W Scheres / Abstract: Intermediate species in the assembly of amyloid filaments are believed to play a central role in neurodegenerative diseases and may constitute important targets for therapeutic intervention. However, ...Intermediate species in the assembly of amyloid filaments are believed to play a central role in neurodegenerative diseases and may constitute important targets for therapeutic intervention. However, structural information about intermediate species has been scarce and the molecular mechanisms by which amyloids assemble remain largely unknown. Here we use time-resolved cryogenic electron microscopy to study the in vitro assembly of recombinant truncated tau (amino acid residues 297-391) into paired helical filaments of Alzheimer's disease or into filaments of chronic traumatic encephalopathy. We report the formation of a shared first intermediate amyloid filament, with an ordered core comprising residues 302-316. Nuclear magnetic resonance indicates that the same residues adopt rigid, β-strand-like conformations in monomeric tau. At later time points, the first intermediate amyloid disappears and we observe many different intermediate amyloid filaments, with structures that depend on the reaction conditions. At the end of both assembly reactions, most intermediate amyloids disappear and filaments with the same ordered cores as those from human brains remain. Our results provide structural insights into the processes of primary and secondary nucleation of amyloid assembly, with implications for the design of new therapies. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_18354.map.gz | 45.9 MB | EMDB map data format | |
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Header (meta data) | emd-18354-v30.xml emd-18354.xml | 14.6 KB 14.6 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_18354_fsc.xml | 13.7 KB | Display | FSC data file |
Images | emd_18354.png | 22.6 KB | ||
Filedesc metadata | emd-18354.cif.gz | 3.9 KB | ||
Others | emd_18354_additional_1.map.gz emd_18354_half_map_1.map.gz emd_18354_half_map_2.map.gz | 198.8 MB 170.6 MB 170.5 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-18354 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-18354 | HTTPS FTP |
-Validation report
Summary document | emd_18354_validation.pdf.gz | 1011.2 KB | Display | EMDB validaton report |
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Full document | emd_18354_full_validation.pdf.gz | 1010.7 KB | Display | |
Data in XML | emd_18354_validation.xml.gz | 21.3 KB | Display | |
Data in CIF | emd_18354_validation.cif.gz | 27.9 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-18354 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-18354 | HTTPS FTP |
-Related structure data
Related structure data | 8ppoC 8q27C 8q2jC 8q2kC 8q2lC 8q7fC 8q7lC 8q7mC 8q7pC 8q7tC 8q88C 8q8cC 8q8dC 8q8eC 8q8fC 8q8lC 8q8mC 8q8rC 8q8sC 8q8uC 8q8vC 8q8wC 8q8xC 8q8yC 8q8zC 8q97C 8q98C 8q99C 8q9aC 8q9bC 8q9cC 8q9dC 8q9eC 8q9fC 8q9gC 8q9hC 8q9iC 8q9jC 8q9kC 8q9lC 8q9mC 8q9oC 8qcpC 8qcrC 8qjjC C: citing same article (ref.) |
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-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_18354.map.gz / Format: CCP4 / Size: 216 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Annotation | Sharpened map | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
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
-Additional map: Unsharpened map
File | emd_18354_additional_1.map | ||||||||||||
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Annotation | Unsharpened map | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half map 1
File | emd_18354_half_map_1.map | ||||||||||||
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Annotation | Half map 1 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half map 2
File | emd_18354_half_map_2.map | ||||||||||||
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Annotation | Half map 2 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Amyloid
Entire | Name: Amyloid |
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Components |
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-Supramolecule #1: Amyloid
Supramolecule | Name: Amyloid / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: Homo sapiens (human) |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | helical reconstruction |
Aggregation state | filament |
-Sample preparation
Buffer | pH: 7.2 |
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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: 2.5 µm / Nominal defocus min: 0.5 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |