8G58

Tau (297-391) in vitro untwisted fibril

Summary for 8G58

• Entry DOI: 10.2210/pdb8g58/pdb
• NMR Information: BMRB: 31059
• Descriptor: Microtubule-associated protein tau (1 entity in total)
• Functional Keywords: ad tau core, untwisted filament, protein fibril
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 10
• Total formula weight: 103188.10

Authors

Duan, P.,Dregni, A.J.,Mammeri, N.E.,Hong, M. (deposition date: 2023-02-12, release date: 2023-11-08, Last modification date: 2024-05-15)

Primary citation

Duan, P.,Dregni, A.J.,Mammeri, N.E.,Hong, M.
Structure of the nonhelical filament of the Alzheimer's disease tau core.
Proc.Natl.Acad.Sci.USA, 120:e2310067120-e2310067120, 2023

PubMed Abstract: The microtubule-associated protein tau aggregates into neurofibrillary tangles in Alzheimer's disease (AD). The main type of aggregates, the paired helical filaments (PHF), incorporate about 20% of the full-length protein into the rigid core. Recently, cryo-electron microscopy data showed that a protease-resistant fragment of tau (residues 297-391) self-assembles in vitro in the presence of divalent cations to form twisted filaments whose molecular structure resembles that of AD PHF tau [S. Lövestam , e76494 (2022)]. To investigate whether this tau construct is uniquely predisposed to this morphology and structure, we fibrillized tau (297-391) under the reported conditions and determined its structure using solid-state NMR spectroscopy. Unexpectedly, the protein assembled predominantly into nontwisting ribbons whose rigid core spans residues 305-357. This rigid core forms a β-arch that turns at residues CGS. Two protofilaments stack together via a long interface that stretches from G323 to I354. Together, these two protofilaments form a four-layered β-sheet core whose sidechains are stabilized by numerous polar and hydrophobic interactions. This structure gives insight into the fibril morphologies and molecular conformations that can be adopted by this protease-resistant core of AD tau under different pH and ionic conditions.

PubMed: 37878719
DOI: 10.1073/pnas.2310067120

Experimental method

SOLID-STATE NMR