Inclusion of the C-Terminal Domain in the β-Sheet Core of Heparin-Fibrillized Three-Repeat Tau Protein Revealed by Solid-State Nuclear Magnetic Resonance Spectroscopy.

ABSTRACT: Many neurodegenerative diseases such as Alzheimer's disease are characterized by pathological β-sheet filaments of the tau protein, which spread in a prion-like manner in patient brains. To date, high-resolution structures of tau filaments obtained from patient brains show that the β-sheet core only includes portions of the microtubule-binding repeat domains and excludes the C-terminal residues, indicating that the C-terminus is dynamically disordered. Here, we use solid-state NMR spectroscopy to identify the β-sheet core of full-length 0N3R tau fibrillized using heparin. Assignment of ¹³C and ¹⁵N chemical shifts of the rigid core of the protein revealed a single predominant β-sheet conformation, which spans not only the R3, R4, R' repeats but also the entire C-termin

SUBMITTER: Dregni AJ 

PROVIDER: S-EPMC8283780 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature