Structure of the Fmoc-Tau-PAM4 Type 2 amyloid fibril

Experimental Data Snapshot

  • Resolution: 2.80 Å
  • Aggregation State: FILAMENT 
  • Reconstruction Method: HELICAL 

wwPDB Validation   3D Report Full Report

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Local structural preferences in shaping tau amyloid polymorphism.

Louros, N.Wilkinson, M.Tsaka, G.Ramakers, M.Morelli, C.Garcia, T.Gallardo, R.D'Haeyer, S.Goossens, V.Audenaert, D.Thal, D.R.Mackenzie, I.R.Rademakers, R.Ranson, N.A.Radford, S.E.Rousseau, F.Schymkowitz, J.

(2024) Nat Commun 15: 1028-1028

  • DOI: https://doi.org/10.1038/s41467-024-45429-2
  • Primary Citation of Related Structures:  
    8OH2, 8OHI, 8OHP, 8OI0

  • PubMed Abstract: 

    Tauopathies encompass a group of neurodegenerative disorders characterised by diverse tau amyloid fibril structures. The persistence of polymorphism across tauopathies suggests that distinct pathological conditions dictate the adopted polymorph for each disease. However, the extent to which intrinsic structural tendencies of tau amyloid cores contribute to fibril polymorphism remains uncertain. Using a combination of experimental approaches, we here identify a new amyloidogenic motif, PAM4 (Polymorphic Amyloid Motif of Repeat 4), as a significant contributor to tau polymorphism. Calculation of per-residue contributions to the stability of the fibril cores of different pathologic tau structures suggests that PAM4 plays a central role in preserving structural integrity across amyloid polymorphs. Consistent with this, cryo-EM structural analysis of fibrils formed from a synthetic PAM4 peptide shows that the sequence adopts alternative structures that closely correspond to distinct disease-associated tau strains. Furthermore, in-cell experiments revealed that PAM4 deletion hampers the cellular seeding efficiency of tau aggregates extracted from Alzheimer's disease, corticobasal degeneration, and progressive supranuclear palsy patients, underscoring PAM4's pivotal role in these tauopathies. Together, our results highlight the importance of the intrinsic structural propensity of amyloid core segments to determine the structure of tau in cells, and in propagating amyloid structures in disease.

  • Organizational Affiliation

    Switch Laboratory, VIB Center for Brain and Disease Research, Herestraat 49, 3000, Leuven, Belgium.


Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Microtubule-associated protein tau
A, B, C, D, E
A, B, C, D, E, F, G, H, I, J, K, L, M, N, O, P, Q, R
14synthetic constructMutation(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
  • Reference Sequence
Small Molecules
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
Query on HIA
A, B, C, D, E
A, B, C, D, E, F, G, H, I, J, K, L, M, N, O, P, Q, R
Experimental Data & Validation

Experimental Data

  • Resolution: 2.80 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
Research Foundation - Flanders (FWO)Belgium--

Revision History  (Full details and data files)

  • Version 1.0: 2024-02-21
    Type: Initial release