Journal Article

DZNE-2023-00955

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Acetylation discriminates disease-specific tau deposition.

Chakraborty, P. (First author)DZNE* ; Rivière, G.DZNE* ; Hebestreit, A.DZNE* ; de Opakua, A. I.DZNE* ; Vorberg, I. M.DZNE* ; Andreas, L. B. ; Zweckstetter, M. (Last author)DZNE*

2023
Nature Publishing Group UK [London]

This record in other databases:    

Please use a persistent id in citations: doi:10.1038/s41467-023-41672-1

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.

Keyword(s): Humans (MeSH) ; 14-3-3 Proteins (MeSH) ; Acetylation (MeSH) ; Alzheimer Disease (MeSH) ; tau Proteins (MeSH) ; Tauopathies (MeSH) ; 14-3-3 Proteins ; tau Proteins ; MAPT protein, human

---

Contributing Institute(s):

1. Translational Structural Biology (AG Zweckstetter)
2. Prion Cell Biology (AG Vorberg)

Research Program(s):

1. 352 - Disease Mechanisms (POF4-352) (POF4-352)

Appears in the scientific report 2023

---

Database coverage:
; ; ; ; Article Processing Charges ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Agriculture, Biology and Environmental Sciences ; Current Contents - Life Sciences ; Current Contents - Physical, Chemical and Earth Sciences ; DOAJ Seal ; Essential Science Indicators ; Fees ; IF >= 15 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection ; Zoological Record

---