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Open data
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Basic information
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Title | CTE Tau intermediate amyloid (LIA-9) | |||||||||
![]() | Sharpened map | |||||||||
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![]() | Amyloid / tau / PROTEIN FIBRIL | |||||||||
Biological species | ![]() | |||||||||
Method | helical reconstruction / cryo EM / Resolution: 5.97 Å | |||||||||
![]() | Lovestam S / Li D / Scheres SHW / Goedert M | |||||||||
Funding support | ![]()
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![]() | ![]() 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. | |||||||||
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Structure visualization
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Downloads & links
-EMDB archive
Map data | ![]() | 46.9 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 14.6 KB 14.6 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 13.7 KB | Display | ![]() |
Images | ![]() | 21 KB | ||
Filedesc metadata | ![]() | 3.9 KB | ||
Others | ![]() ![]() ![]() | 172.5 MB 172.6 MB 172.4 MB | ||
Archive directory | ![]() ![]() | 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 ( |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Annotation | Sharpened map | ||||||||||||||||||||
Voxel size | X=Y=Z: 0.824 Å | ||||||||||||||||||||
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Additional map: Unsharpened map
File | emd_18361_additional_1.map | ||||||||||||
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Annotation | Unsharpened map | ||||||||||||
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Density Histograms |
-Half map: Half map 1
File | emd_18361_half_map_1.map | ||||||||||||
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Annotation | Half map 1 | ||||||||||||
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Density Histograms |
-Half map: Half map 2
File | emd_18361_half_map_2.map | ||||||||||||
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Annotation | Half map 2 | ||||||||||||
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Density Histograms |
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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: ![]() |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | helical reconstruction |
Aggregation state | filament |
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Sample preparation
Buffer | pH: 7.2 |
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Vitrification | Cryogen name: ETHANE |
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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: ![]() |
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 |