[200221 저널발표] Posttranslational Modifications Mediate the Structural Diversity of Tauopathy Strains.
최현정 │ 2020-02-18
Cell. 2020 Feb 3. pii: S0092-8674(20)30108-2. doi: 10.1016/j.cell.2020.01.027. [Epub ahead of print]
Posttranslational Modifications Mediate the Structural Diversity of Tauopathy Strains.
Arakhamia T1, Lee CE1, Carlomagno Y2, Duong DM3, Kundinger SR3, Wang K1, Williams D4, DeTure M2, Dickson DW2, Cook CN2, Seyfried NT5, Petrucelli L6, Fitzpatrick AWP7.
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.
|Prev||[200207 저널발표] The epichaperome is a mediator of toxic hippocampal stress and...|
|Next||[200221 저널발표] Lipid-droplet-accumulating Microglia Represent a Dysfunctional...|