6VI3

Straight Filament from Alzheimer's Disease Human Brain Tissue

Summary for 6VI3

• Entry DOI: 10.2210/pdb6vi3/pdb
• Related: 6VI3
• EMDB information: 0260
• Descriptor: Microtubule-associated protein tau, GLYCINE (2 entities in total)
• Functional Keywords: pathological amyloid fibril cross-beta fold parallel beta-sheets, protein fibril
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 16891.29

Authors

Arakhamia, T.,Lee, C.E.,Carlomagno, Y.,Duong, D.M.,Kundinger, S.R.,Wang, K.,Williams, D.,DeTure, M.,Dickson, D.W.,Cook, C.N.,Seyfried, N.T.,Petrucelli, L.,Fitzpatrick, A.W.P. (deposition date: 2020-01-11, release date: 2020-04-15, Last modification date: 2024-03-06)

Primary citation

Arakhamia, T.,Lee, C.E.,Carlomagno, Y.,Duong, D.M.,Kundinger, S.R.,Wang, K.,Williams, D.,DeTure, M.,Dickson, D.W.,Cook, C.N.,Seyfried, N.T.,Petrucelli, L.,Fitzpatrick, A.W.P.
Posttranslational Modifications Mediate the Structural Diversity of Tauopathy Strains
Cell, 180:633-644.e12, 2020

PubMed Abstract: Tau aggregation into insoluble filaments is the defining pathological hallmark of tauopathies. However, it is not known what controls the formation and templated seeding of strain-specific structures associated with individual tauopathies. Here, we use cryo-electron microscopy (cryo-EM) to determine the structures of tau filaments from corticobasal degeneration (CBD) human brain tissue. Cryo-EM and mass spectrometry of tau filaments from CBD reveal that this conformer is heavily decorated with posttranslational modifications (PTMs), enabling us to map PTMs directly onto the structures. By comparing the structures and PTMs of tau filaments from CBD and Alzheimer's disease, it is found that ubiquitination of tau can mediate inter-protofilament interfaces. We propose a structure-based model in which cross-talk between PTMs influences tau filament structure, contributing to the structural diversity of tauopathy strains. Our approach establishes a framework for further elucidating the relationship between the structures of polymorphic fibrils, including their PTMs, and neurodegenerative disease.

PubMed: 32032505
DOI: 10.1016/j.cell.2020.01.027

Experimental method

ELECTRON MICROSCOPY (3.3 Å)