Journal
FRONTIERS IN NEUROSCIENCE
Volume 16, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fnins.2022.988074
Keywords
tau protein; solid-state NMR; amyloid structure; neurodegenerative diseases; Alzheimer's disease
Categories
Funding
- National Institutes of Health
- WisTa Laboratories Ltd.
- [R01AG061865]
- [R01NS120704]
Ask authors/readers for more resources
Aggregation of the tau protein into fibrillar cross-beta aggregates is a characteristic of neurodegenerative diseases like Alzheimer's disease. A recent study found that a tau fragment called dGAE can form filaments in vitro, providing a promising model for studying AD tau filaments. Solid-state NMR was used to characterize the tau filaments and it was found that filaments assembled under non-reducing conditions are more dynamic and less ordered than those assembled in the presence of a reducing agent.
Aggregation of the tau protein into fibrillar cross-beta aggregates is a hallmark of Alzheimer's diseases (AD) and many other neurodegenerative tauopathies. Recently, several core structures of patient-derived tau paired helical filaments (PHFs) have been solved revealing a structural variability that often correlates with a specific tauopathy. To further characterize the dynamics of these fibril cores, to screen for strain-specific small molecules as potential biomarkers and therapeutics, and to develop strain-specific antibodies, recombinant in-vitro models of tau filaments are needed. We recently showed that a 95-residue fragment of tau (from residue 297 to 391), termed dGAE, forms filaments in vitro in the absence of polyanionic co-factors often used for in vitro aggregation of full-length tau. Tau(297-391) was identified as the proteolytic resistant core of tau PHFs and overlaps with the structures characterized by cryo-electron microscopy in ex vivo PHFs, making it a promising model for the study of AD tau filaments in vitro. In the present study, we used solid-state NMR to characterize tau(297-391) filaments and show that such filaments assembled under non-reducing conditions are more dynamic and less ordered than those made in the presence of the reducing agent DTT. We further report the resonance assignment of tau(297-391)+DTT filaments and compare it to existing core structures of tau.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available