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  Solid-state NMR investigation of the involvement of the P2 region in tau amyloid fibrils

Savastano, A., Jaipuria, G., Andreas, L. B., Mandelkow, E., & Zweckstetter, M. (2020). Solid-state NMR investigation of the involvement of the P2 region in tau amyloid fibrils. Scientific Reports, 10: 21210. doi:10.1038/s41598-020-78161-0.

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 Creators:
Savastano, A.1, Author              
Jaipuria, G., Author
Andreas, L. B.2, Author              
Mandelkow, E., Author
Zweckstetter, M.3, Author              
Affiliations:
1Research Group of Protein Structure Determination using NMR, MPI for Biophysical Chemistry, Max Planck Society, ou_578571              
2Research Group of Solid State NMR Spectroscopy-2, MPI for Biophysical Chemistry, Max Planck Society, ou_2396693              
3Research Group of Protein Structure Determination using NMR, MPI for biophysical chemistry, Max Planck Society, ou_578571              

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Free keywords: Biophysics; Intrinsically disordered proteins; NMR spectroscopy; Proteins
 Abstract: The aggregation of hyperphosphorylated tau into amyloid fibrils is closely linked to the progression of Alzheimer’s disease. To gain insight into the link between amyloid structure and disease, the three-dimensional structure of tau fibrils has been studied using solid-state NMR (ssNMR) and cryogenic electron microscopy (cryo-EM). The proline-rich region of tau remains poorly defined in the context of tau amyloid structures, despite the clustering of several phosphorylation sites, which have been associated with Alzheimer’s disease. In order to gain insight into the contribution of the proline-rich region P2 of tau to amyloid fibrils, we studied in vitro aggregated amyloid fibrils of tau constructs, which contain both the proline-rich region P2 and the pseudo-repeats. Using ssNMR we show that the sequence 225KVAVVRT231, the most hydrophobic patch within the P2 region, loses its flexibility upon formation of amyloid fibrils. The data suggest a contribution of the P2 region to tau amyloid fibril formation, which might account for some of the unassigned electron density in cryo-EM studies of tau fibrils and could be modulated by tau phosphorylation at the disease-associated AT180 epitope T231/S235.

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Language(s): eng - English
 Dates: 2020-12-03
 Publication Status: Published online
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 Rev. Type: Peer
 Identifiers: DOI: 10.1038/s41598-020-78161-0
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Title: Scientific Reports
Source Genre: Journal
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Pages: 14 Volume / Issue: 10 Sequence Number: 21210 Start / End Page: - Identifier: -