Acetylation discriminates disease-specific tau deposition
2023 | journal article. A publication with affiliation to the University of Göttingen.
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Acetylation discriminates disease-specific tau deposition
Chakraborty, P.; Rivière, G.; Hebestreit, A.; de Opakua, A. I.; Vorberg, I. M.; Andreas, L. B. & Zweckstetter, M. (2023)
Nature Communications, 14(1). DOI: https://doi.org/10.1038/s41467-023-41672-1
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Details
- Authors
- Chakraborty, Pijush; Rivière, Gwladys; Hebestreit, Alina; de Opakua, Alain Ibáñez; Vorberg, Ina M.; Andreas, Loren B.; Zweckstetter, Markus
- Abstract
- Abstract Pathogenic aggregation of the protein tau is a hallmark of Alzheimer’s disease and several other tauopathies. Tauopathies are characterized by the deposition of specific tau isoforms as disease-related tau filament structures. The molecular processes that determine isoform-specific deposition of tau are however enigmatic. Here we show that acetylation of tau discriminates its isoform-specific aggregation. We reveal that acetylation strongly attenuates aggregation of four-repeat tau protein, but promotes amyloid formation of three-repeat tau. We further identify acetylation of lysine 298 as a hot spot for isoform-specific tau aggregation. Solid-state NMR spectroscopy demonstrates that amyloid fibrils formed by unmodified and acetylated three-repeat tau differ in structure indicating that site-specific acetylation modulates tau structure. The results implicate acetylation as a critical regulator that guides the selective aggregation of three-repeat tau and the development of tau isoform-specific neurodegenerative diseases.
- Issue Date
- 2023
- Journal
- Nature Communications
- eISSN
- 2041-1723
- Language
- English