% IMPORTANT: The following is UTF-8 encoded. This means that in the presence % of non-ASCII characters, it will not work with BibTeX 0.99 or older. % Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or % “biber”. @ARTICLE{Chakraborty:264175, author = {Chakraborty, Pijush and Rivière, Gwladys and Hebestreit, Alina and de Opakua, Alain Ibáñez and Vorberg, Ina M and Andreas, Loren B and Zweckstetter, Markus}, title = {{A}cetylation discriminates disease-specific tau deposition.}, journal = {Nature Communications}, volume = {14}, number = {1}, issn = {2041-1723}, address = {[London]}, publisher = {Nature Publishing Group UK}, reportid = {DZNE-2023-00955}, pages = {5919}, year = {2023}, 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.}, keywords = {Humans / 14-3-3 Proteins / Acetylation / Alzheimer Disease / tau Proteins / Tauopathies / 14-3-3 Proteins (NLM Chemicals) / tau Proteins (NLM Chemicals) / MAPT protein, human (NLM Chemicals)}, cin = {AG Zweckstetter / AG Vorberg}, ddc = {500}, cid = {I:(DE-2719)1410001 / I:(DE-2719)1013004}, pnm = {352 - Disease Mechanisms (POF4-352)}, pid = {G:(DE-HGF)POF4-352}, typ = {PUB:(DE-HGF)16}, pubmed = {pmid:37739953}, pmc = {pmc:PMC10517010}, doi = {10.1038/s41467-023-41672-1}, url = {https://pub.dzne.de/record/264175}, }