Tau - CTE-LIA14 (tau intermediate amyloid)

Experimental Data Snapshot

  • Resolution: 2.76 Å
  • Aggregation State: FILAMENT 
  • Reconstruction Method: HELICAL 

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This is version 1.3 of the entry. See complete history


Disease-specific tau filaments assemble via polymorphic intermediates.

Lovestam, S.Li, D.Wagstaff, J.L.Kotecha, A.Kimanius, D.McLaughlin, S.H.Murzin, A.G.Freund, S.M.V.Goedert, M.Scheres, S.H.W.

(2024) Nature 625: 119-125

  • DOI: https://doi.org/10.1038/s41586-023-06788-w
  • Primary Citation of Related Structures:  
    8PPO, 8Q27, 8Q2J, 8Q2K, 8Q2L, 8Q7F, 8Q7L, 8Q7M, 8Q7P, 8Q7T, 8Q88, 8Q8C, 8Q8D, 8Q8E, 8Q8F, 8Q8L, 8Q8M, 8Q8R, 8Q8S, 8Q8U, 8Q8V, 8Q8W, 8Q8X, 8Q8Y, 8Q8Z, 8Q97, 8Q98, 8Q99, 8Q9A, 8Q9B, 8Q9C, 8Q9D, 8Q9E, 8Q9F, 8Q9G, 8Q9H, 8Q9I, 8Q9J, 8Q9K, 8Q9L, 8Q9M, 8Q9O, 8QCP, 8QCR, 8QJJ

  • PubMed 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 1,2 . 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 3 . 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.

  • Organizational Affiliation

    MRC Laboratory of Molecular Biology, Cambridge, UK.

Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Isoform Tau-D of Microtubule-associated protein tau382Homo sapiensMutation(s): 0 
Gene Names: MAPT
UniProt & NIH Common Fund Data Resources
Find proteins for P10636 (Homo sapiens)
Explore P10636 
Go to UniProtKB:  P10636
GTEx:  ENSG00000186868 
Entity Groups  
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UniProt GroupP10636
Sequence Annotations
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Resolution: 2.76 Å
  • Aggregation State: FILAMENT 
  • Reconstruction Method: HELICAL 
EM Software:
TaskSoftware PackageVersion

Structure Validation

View Full Validation Report

Entry History & Funding Information

Deposition Data

Funding OrganizationLocationGrant Number
Medical Research Council (MRC, United Kingdom)United Kingdom--

Revision History  (Full details and data files)

  • Version 1.0: 2023-09-06
    Type: Initial release
  • Version 1.1: 2023-12-06
    Changes: Database references
  • Version 1.2: 2023-12-13
    Changes: Database references
  • Version 1.3: 2024-01-17
    Changes: Database references