Pseudo-Phosphorylated Tau Forms Paired Helical Filaments in the Presence of High-Curvature Cholesterol-Containing Lipid Membranes.

ABSTRACT: The tau protein misfolds in neurodegenerative diseases such as Alzheimer's disease (AD). These pathological tau aggregates are associated with neuronal membranes, but molecular structural information about how disease-like tau fibrils interact with the lipid membrane is scarce. Here, we use solid-state NMR to investigate the structure of a tau construct bearing four AD-relevant phospho-mimetic mutations (4E tau) with cholesterol-containing high-curvature lipid membranes, which mimic the membrane of synaptic vesicles in neurons. We show that 4E tau adopts the AD paired helical filament (PHF) fold in the presence of the membrane at high protein concentrations. Moreover, it inserts into the membrane-water interface with an orientation that suggests possible bridging of multiple lipid vesicles

SUBMITTER: El Mammeri N 

PROVIDER: S-EPMC12225538 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature