Heterogeneous Dynamics of the Fuzzy Coat of Full-Length Phospho-Mimetic Tau Fibrils
Massachusetts Institute of Technology
Abstract
The β-sheet core of many amyloid proteins in neurodegenerative diseases is surrounded by dynamically disordered segments that contact cellular species. Recent data suggest that this "fuzzy coat" may also regulate the prion-like propagation of amyloid proteins. Here we report the site-specific dynamics of the fuzzy coat of a full-length tau fibril, assembled without anionic cofactors in the presence of four phospho-mimetic glutamate mutations at the PHF1 epitope of Alzheimer's disease tau. The rigid core structure of this 4E tau was recently determined to consist of three β-strands, resembling the structure of three-layered tau aggregates in certain tauopathies. Using solid-state and solution NMR, we measured…
Citation impact
- FWCI
- 72.49
- Percentile
- 100%
- References
- 62
Authors
3Topics & keywords
- Fibril
- Molecular dynamics
- Amyloid (mycology)
- Fuzzy logic
- Amyloid fibril
- Protein structure
- Coat
- Intrinsically disordered proteins