Reconstitution of the Alzheimer's Disease Tau Core Structure from Recombinant Tau^297-391 Yields Variable Quaternary Structures as Seen by Negative Stain and Cryo-EM.

ABSTRACT: The protein tau misfolds into disease-specific fibrillar structures in more than 20 neurodegenerative diseases collectively referred to as tauopathies. To understand and prevent disease-specific mechanisms of filament formation, in vitro models for aggregation that robustly yield these different end point structures will be necessary. Here, we used cryo-electron microscopy (cryo-EM) to reconstruct fibril polymorphs taken on by residues 297-391 of tau under conditions previously shown to give rise to the core structure found in Alzheimer's disease (AD). While we were able to reconstitute the AD tau core fold, the proportion of these paired helical filaments (PHFs) was highly variable, and a majority of filaments were composed of PHFs with an additional identical C-shaped protofilamen

SUBMITTER: Glynn C 

PROVIDER: S-EPMC10795186 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature