%0 Journal Article
%A Chakraborty, Pijush
%A Rivière, Gwladys
%A Hebestreit, Alina
%A de Opakua, Alain Ibáñez
%A Vorberg, Ina M
%A Andreas, Loren B
%A Zweckstetter, Markus
%T Acetylation discriminates disease-specific tau deposition.
%J Nature Communications
%V 14
%N 1
%@ 2041-1723
%C [London]
%I Nature Publishing Group UK
%M DZNE-2023-00955
%P 5919
%D 2023
%X 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.
%K Humans
%K 14-3-3 Proteins
%K Acetylation
%K Alzheimer Disease
%K tau Proteins
%K Tauopathies
%K 14-3-3 Proteins (NLM Chemicals)
%K tau Proteins (NLM Chemicals)
%K MAPT protein, human (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:37739953
%2 pmc:PMC10517010
%R 10.1038/s41467-023-41672-1
%U https://pub.dzne.de/record/264175