6HRF

Straight filament from sporadic Alzheimer's disease brain


Experimental Data Snapshot

  • Method: ELECTRON MICROSCOPY
  • Resolution: 3.30 Å
  • Aggregation State: TISSUE 
  • Reconstruction Method: HELICAL 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Tau filaments from multiple cases of sporadic and inherited Alzheimer's disease adopt a common fold.

Falcon, B.Zhang, W.Schweighauser, M.Murzin, A.G.Vidal, R.Garringer, H.J.Ghetti, B.Scheres, S.H.W.Goedert, M.

(2018) Acta Neuropathol 136: 699-708

  • DOI: https://doi.org/10.1007/s00401-018-1914-z
  • Primary Citation of Related Structures:  
    6HRE, 6HRF

  • PubMed Abstract: 

    The ordered assembly of tau protein into abnormal filaments is a defining characteristic of Alzheimer's disease (AD) and other neurodegenerative disorders. It is not known if the structures of tau filaments vary within, or between, the brains of individuals with AD. We used a combination of electron cryo-microscopy (cryo-EM) and immuno-gold negative-stain electron microscopy (immuno-EM) to determine the structures of paired helical filaments (PHFs) and straight filaments (SFs) from the frontal cortex of 17 cases of AD (15 sporadic and 2 inherited) and 2 cases of atypical AD (posterior cortical atrophy). The high-resolution structures of PHFs and SFs from the frontal cortex of 3 cases of AD, 2 sporadic and 1 inherited, were determined by cryo-EM. We also used immuno-EM to study the PHFs and SFs from a number of cortical and subcortical brain regions. PHFs outnumbered SFs in all AD cases. By cryo-EM, PHFs and SFs were made of two C-shaped protofilaments with a combined cross-β/β-helix structure, as described previously for one case of AD. The higher resolution structures obtained here showed two additional amino acids at each end of the protofilament. The immuno-EM findings, which indicated the presence of repeats 3 and 4, but not of the N-terminal regions of repeats 1 and 2, of tau in the filament cores of all AD cases, were consistent with the cryo-EM results. These findings show that there is no significant variation in tau filament structures between individuals with AD. This knowledge will be crucial for understanding the mechanisms that underlie tau filament formation and for developing novel diagnostics and therapies.


  • Organizational Affiliation

    MRC Laboratory of Molecular Biology, Cambridge, CB2 0QH, UK.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Microtubule-associated protein tau
A, B, C, D, E
A, B, C, D, E, F
441Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for P10636 (Homo sapiens)
Explore P10636 
Go to UniProtKB:  P10636
PHAROS:  P10636
GTEx:  ENSG00000186868 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP10636
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: ELECTRON MICROSCOPY
  • Resolution: 3.30 Å
  • Aggregation State: TISSUE 
  • Reconstruction Method: HELICAL 
EM Software:
TaskSoftware PackageVersion
RECONSTRUCTIONRELION2.1
MODEL REFINEMENTREFMAC5.7.0032

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Medical Research Council (United Kingdom)United KingdomMC_U105184291
Medical Research Council (United Kingdom)United KingdomMC_UP_A025_1013
National Institutes of Health/National Institute on Aging (NIH/NIA)United StatesP30-AG010133
European UnionUnited KingdomJoint Programme-Neurodegeneration Research
European UnionUnited KingdomHorizon 2020 IMPRiND

Revision History  (Full details and data files)

  • Version 1.0: 2018-10-10
    Type: Initial release
  • Version 1.1: 2018-11-07
    Changes: Data collection, Database references, Structure summary
  • Version 1.2: 2019-12-18
    Changes: Other
  • Version 1.3: 2022-03-30
    Changes: Author supporting evidence, Database references