1H detection and dynamic nuclear polarization–enhanced NMR of Aβ1-42 fibrils
Name
pnas.2114413119.pdf
Description
Published version
Size
3.22 MB
Format
Adobe PDF
Checksum (MD5)
545b18e651940276a0a8ce2bc1651265
Author(s)
Bahri, Salima
Silvers, Robert
Michael, Brian
Jaudzems, Kristaps
Lalli, Daniela
Casano, Gilles
Ouari, Olivier
Lesage, Anne
Pintacuda, Guido
Linse, Sara
Date Issued
January 4, 2022
Journal
Proceedings of the National Academy of Sciences
Publisher
Proceedings of the National Academy of Sciences
Citation
Bahri, Salima, Silvers, Robert, Michael, Brian, Jaudzems, Kristaps, Lalli, Daniela et al. 2022. "1H detection and dynamic nuclear polarization–enhanced NMR of Aβ1-42 fibrils." Proceedings of the National Academy of Sciences, 119 (1).
Version
Final published version
Abstract
Several publications describing high-resolution structures of amyloid-β (Aβ) and other fibrils have demonstrated that magic-angle spinning (MAS) NMR spectroscopy is an ideal tool for studying amyloids at atomic resolution. Nonetheless, MAS NMR suffers from low sensitivity, requiring relatively large amounts of samples and extensive signal acquisition periods, which in turn limits the questions that can be addressed by atomic-level spectroscopic studies. Here, we show that these drawbacks are removed by utilizing two relatively recent additions to the repertoire of MAS NMR experiments—namely, 1H detection and dynamic nuclear polarization (DNP). We show resolved and sensitive two-dimensional (2D) and three-dimensional (3D) correlations obtained on 13C,15N-enriched, and fully protonated samples of M0Aβ1-42 fibrils by high-field 1H-detected NMR at 23.4 T and 18.8 T, and 13C-detected DNP MAS NMR at 18.8 T. These spectra enable nearly complete resonance assignment of the core of M0Aβ1-42 (K16-A42) using submilligram sample quantities, as well as the detection of numerous unambiguous internuclear proximities defining both the structure of the core and the arrangement of the different monomers. An estimate of the sensitivity of the two approaches indicates that the DNP experiments are currently ∼6.5 times more sensitive than 1H detection. These results suggest that 1H detection and DNP may be the spectroscopic approaches of choice for future studies of Aβ and other amyloid systems.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
Francis Bitter Magnet Laboratory (Massachusetts Institute of Technology)
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DOI of Published Version
https://doi.org/10.1073/pnas.2114413119
