1H detection and dynamic nuclear polarization–enhanced NMR of Aβ1-42 fibrils
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...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Proceedings of the National Academy of Sciences
2022
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| Online Access: | https://hdl.handle.net/1721.1/141068 |
| _version_ | 1826188248877105152 |
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| author | Bahri, Salima Silvers, Robert Michael, Brian Jaudzems, Kristaps Lalli, Daniela Casano, Gilles Ouari, Olivier Lesage, Anne Pintacuda, Guido Linse, Sara Griffin, Robert G |
| author2 | Massachusetts Institute of Technology. Department of Chemistry |
| author_facet | Massachusetts Institute of Technology. Department of Chemistry Bahri, Salima Silvers, Robert Michael, Brian Jaudzems, Kristaps Lalli, Daniela Casano, Gilles Ouari, Olivier Lesage, Anne Pintacuda, Guido Linse, Sara Griffin, Robert G |
| author_sort | Bahri, Salima |
| collection | MIT |
| description | 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, <jats:sup>1</jats:sup>H detection and dynamic nuclear polarization (DNP). We show resolved and sensitive two-dimensional (2D) and three-dimensional (3D) correlations obtained on <jats:sup>13</jats:sup>C,<jats:sup>15</jats:sup>N-enriched, and fully protonated samples of M<jats:sub>0</jats:sub>Aβ<jats:sub>1-42</jats:sub> fibrils by high-field <jats:sup>1</jats:sup>H-detected NMR at 23.4 T and 18.8 T, and <jats:sup>13</jats:sup>C-detected DNP MAS NMR at 18.8 T. These spectra enable nearly complete resonance assignment of the core of M<jats:sub>0</jats:sub>Aβ<jats:sub>1-42</jats:sub> (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 <jats:sup>1</jats:sup>H detection. These results suggest that <jats:sup>1</jats:sup>H detection and DNP may be the spectroscopic approaches of choice for future studies of Aβ and other amyloid systems. |
| first_indexed | 2024-09-23T07:56:30Z |
| format | Article |
| id | mit-1721.1/141068 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T07:56:30Z |
| publishDate | 2022 |
| publisher | Proceedings of the National Academy of Sciences |
| record_format | dspace |
| spelling | mit-1721.1/1410682023-03-28T20:13:04Z 1H detection and dynamic nuclear polarization–enhanced NMR of Aβ1-42 fibrils Bahri, Salima Silvers, Robert Michael, Brian Jaudzems, Kristaps Lalli, Daniela Casano, Gilles Ouari, Olivier Lesage, Anne Pintacuda, Guido Linse, Sara Griffin, Robert G Massachusetts Institute of Technology. Department of Chemistry Francis Bitter Magnet Laboratory (Massachusetts Institute of Technology) 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, <jats:sup>1</jats:sup>H detection and dynamic nuclear polarization (DNP). We show resolved and sensitive two-dimensional (2D) and three-dimensional (3D) correlations obtained on <jats:sup>13</jats:sup>C,<jats:sup>15</jats:sup>N-enriched, and fully protonated samples of M<jats:sub>0</jats:sub>Aβ<jats:sub>1-42</jats:sub> fibrils by high-field <jats:sup>1</jats:sup>H-detected NMR at 23.4 T and 18.8 T, and <jats:sup>13</jats:sup>C-detected DNP MAS NMR at 18.8 T. These spectra enable nearly complete resonance assignment of the core of M<jats:sub>0</jats:sub>Aβ<jats:sub>1-42</jats:sub> (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 <jats:sup>1</jats:sup>H detection. These results suggest that <jats:sup>1</jats:sup>H detection and DNP may be the spectroscopic approaches of choice for future studies of Aβ and other amyloid systems. 2022-03-08T20:24:07Z 2022-03-08T20:24:07Z 2022-01-04 2022-03-08T20:07:47Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/141068 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). en 10.1073/pnas.2114413119 Proceedings of the National Academy of Sciences Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Proceedings of the National Academy of Sciences PNAS |
| spellingShingle | Bahri, Salima Silvers, Robert Michael, Brian Jaudzems, Kristaps Lalli, Daniela Casano, Gilles Ouari, Olivier Lesage, Anne Pintacuda, Guido Linse, Sara Griffin, Robert G 1H detection and dynamic nuclear polarization–enhanced NMR of Aβ1-42 fibrils |
| title | 1H detection and dynamic nuclear polarization–enhanced NMR of Aβ1-42 fibrils |
| title_full | 1H detection and dynamic nuclear polarization–enhanced NMR of Aβ1-42 fibrils |
| title_fullStr | 1H detection and dynamic nuclear polarization–enhanced NMR of Aβ1-42 fibrils |
| title_full_unstemmed | 1H detection and dynamic nuclear polarization–enhanced NMR of Aβ1-42 fibrils |
| title_short | 1H detection and dynamic nuclear polarization–enhanced NMR of Aβ1-42 fibrils |
| title_sort | 1h detection and dynamic nuclear polarization enhanced nmr of aβ1 42 fibrils |
| url | https://hdl.handle.net/1721.1/141068 |
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