Water Distribution, Dynamics, and Interactions with Alzheimer’s β-Amyloid Fibrils Investigated by Solid-State NMR
Water is essential for protein folding and assembly of amyloid fibrils. Internal water cavities have been proposed for several amyloid fibrils, but no direct structural and dynamical data have been reported on the water dynamics and site-specific interactions of water with the fibrils. Here we use s...
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| Format: | Article |
| Language: | en_US |
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American Chemical Society (ACS)
2018
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| Online Access: | http://hdl.handle.net/1721.1/114965 https://orcid.org/0000-0002-1801-924X https://orcid.org/0000-0001-5255-5858 |
| _version_ | 1811089635608100864 |
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| author | Wang, Tuo Jo, Hyunil DeGrado, William F. Hong, Mei |
| author2 | Massachusetts Institute of Technology. Department of Chemistry |
| author_facet | Massachusetts Institute of Technology. Department of Chemistry Wang, Tuo Jo, Hyunil DeGrado, William F. Hong, Mei |
| author_sort | Wang, Tuo |
| collection | MIT |
| description | Water is essential for protein folding and assembly of amyloid fibrils. Internal water cavities have been proposed for several amyloid fibrils, but no direct structural and dynamical data have been reported on the water dynamics and site-specific interactions of water with the fibrils. Here we use solid-state NMR spectroscopy to investigate the water interactions of several Aβ40 fibrils. ¹H spectral lineshapes, T₂ relaxation times, and two-dimensional (2D) ¹H–¹³C correlation spectra show that there are five distinct water pools: three are peptide-bound water, while two are highly dynamic water that can be assigned to interfibrillar water and bulk-like matrix water. All these water pools are associated with the fibrils on the nanometer scale. Water-transferred 2D correlation spectra allow us to map out residue-specific hydration and give evidence for the presence of a water pore in the center of the three-fold symmetric wild-type Aβ40 fibril. In comparison, the loop residues and the intramolecular strand–strand interface have low hydration, excluding the presence of significant water cavities in these regions. The Osaka Aβ40 mutant shows lower hydration and more immobilized water than wild-type Aβ40, indicating the influence of peptide structure on the dynamics and distribution of hydration water. Finally, the highly mobile interfibrillar and matrix water exchange with each other on the time scale of seconds, suggesting that fibril bundling separates these two water pools, and water molecules must diffuse along the fibril axis before exchanging between these two environments. These results provide insights and experimental constraints on the spatial distribution and dynamics of water pools in these amyloid fibrils. |
| first_indexed | 2024-09-23T14:22:20Z |
| format | Article |
| id | mit-1721.1/114965 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T14:22:20Z |
| publishDate | 2018 |
| publisher | American Chemical Society (ACS) |
| record_format | dspace |
| spelling | mit-1721.1/1149652022-09-29T09:01:29Z Water Distribution, Dynamics, and Interactions with Alzheimer’s β-Amyloid Fibrils Investigated by Solid-State NMR Wang, Tuo Jo, Hyunil DeGrado, William F. Hong, Mei Massachusetts Institute of Technology. Department of Chemistry Hong, Mei Wang, Tuo Hong, Mei Water is essential for protein folding and assembly of amyloid fibrils. Internal water cavities have been proposed for several amyloid fibrils, but no direct structural and dynamical data have been reported on the water dynamics and site-specific interactions of water with the fibrils. Here we use solid-state NMR spectroscopy to investigate the water interactions of several Aβ40 fibrils. ¹H spectral lineshapes, T₂ relaxation times, and two-dimensional (2D) ¹H–¹³C correlation spectra show that there are five distinct water pools: three are peptide-bound water, while two are highly dynamic water that can be assigned to interfibrillar water and bulk-like matrix water. All these water pools are associated with the fibrils on the nanometer scale. Water-transferred 2D correlation spectra allow us to map out residue-specific hydration and give evidence for the presence of a water pore in the center of the three-fold symmetric wild-type Aβ40 fibril. In comparison, the loop residues and the intramolecular strand–strand interface have low hydration, excluding the presence of significant water cavities in these regions. The Osaka Aβ40 mutant shows lower hydration and more immobilized water than wild-type Aβ40, indicating the influence of peptide structure on the dynamics and distribution of hydration water. Finally, the highly mobile interfibrillar and matrix water exchange with each other on the time scale of seconds, suggesting that fibril bundling separates these two water pools, and water molecules must diffuse along the fibril axis before exchanging between these two environments. These results provide insights and experimental constraints on the spatial distribution and dynamics of water pools in these amyloid fibrils. National Institutes of Health (U.S.) (Grant GM066976) National Institutes of Health (U.S.) (Grant P01 AG002132) 2018-04-26T15:28:59Z 2018-04-26T15:28:59Z 2017-05 2017-03 Article http://purl.org/eprint/type/JournalArticle 0002-7863 1520-5126 http://hdl.handle.net/1721.1/114965 Wang, Tuo et al. “Water Distribution, Dynamics, and Interactions with Alzheimer’s β-Amyloid Fibrils Investigated by Solid-State NMR.” Journal of the American Chemical Society 139, 17 (April 2017): 6242–6252 © 2017 American Chemical Society https://orcid.org/0000-0002-1801-924X https://orcid.org/0000-0001-5255-5858 en_US http://dx.doi.org/10.1021/jacs.7b02089 Journal of the American Chemical Society 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 American Chemical Society (ACS) Prof. Hong via Erja Kajosalo |
| spellingShingle | Wang, Tuo Jo, Hyunil DeGrado, William F. Hong, Mei Water Distribution, Dynamics, and Interactions with Alzheimer’s β-Amyloid Fibrils Investigated by Solid-State NMR |
| title | Water Distribution, Dynamics, and Interactions with Alzheimer’s β-Amyloid Fibrils Investigated by Solid-State NMR |
| title_full | Water Distribution, Dynamics, and Interactions with Alzheimer’s β-Amyloid Fibrils Investigated by Solid-State NMR |
| title_fullStr | Water Distribution, Dynamics, and Interactions with Alzheimer’s β-Amyloid Fibrils Investigated by Solid-State NMR |
| title_full_unstemmed | Water Distribution, Dynamics, and Interactions with Alzheimer’s β-Amyloid Fibrils Investigated by Solid-State NMR |
| title_short | Water Distribution, Dynamics, and Interactions with Alzheimer’s β-Amyloid Fibrils Investigated by Solid-State NMR |
| title_sort | water distribution dynamics and interactions with alzheimer s β amyloid fibrils investigated by solid state nmr |
| url | http://hdl.handle.net/1721.1/114965 https://orcid.org/0000-0002-1801-924X https://orcid.org/0000-0001-5255-5858 |
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