Observation of β-Amyloid Peptide Oligomerization by Pressure-Jump NMR Spectroscopy
(2019) In Journal of the American Chemical Society 141(35). p.13762-13766- Abstract
- Brain tissue of Alzheimer’s disease patients invariably contains deposits of insoluble, fibrillar aggregates of peptide fragments of the amyloid precursor protein (APP), typically 40 or 42 residues in length and referred to as Aβ40 and Aβ42. However, it remains unclear whether these fibrils or oligomers constitute the toxic species. Depending on sample conditions, oligomers can form in a few seconds or less. These oligomers are invisible to solution NMR spectroscopy, but they can be rapidly (<1 s) resolubilized and converted to their NMR-visible monomeric constituents by raising the hydrostatic pressure to a few kbar. Hence, utilizing pressure-jump NMR, the oligomeric state can be studied at residue-specific resolution by monitoring its... (More)
- Brain tissue of Alzheimer’s disease patients invariably contains deposits of insoluble, fibrillar aggregates of peptide fragments of the amyloid precursor protein (APP), typically 40 or 42 residues in length and referred to as Aβ40 and Aβ42. However, it remains unclear whether these fibrils or oligomers constitute the toxic species. Depending on sample conditions, oligomers can form in a few seconds or less. These oligomers are invisible to solution NMR spectroscopy, but they can be rapidly (<1 s) resolubilized and converted to their NMR-visible monomeric constituents by raising the hydrostatic pressure to a few kbar. Hence, utilizing pressure-jump NMR, the oligomeric state can be studied at residue-specific resolution by monitoring its signals in the monomeric state. Oligomeric states of Aβ40 exhibit a high degree of order, reflected by slow longitudinal 15N relaxation (T1 > 5 s) for residues 18–21 and 31–34, whereas the N-terminal 10 residues relax much faster (T1 ≤ 1.5 s), indicative of extensive internal motions. Transverse relaxation rates rapidly increase to ca. 1000 s–1 after the oligomerization is initiated. (Less)
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https://lup.lub.lu.se/record/5ac08dbe-5865-4322-bb1d-a91af8101d1c
- author
- Barnes, C. Ashley ; Robertson, Angus J. LU ; Louis, John M. ; Anfinrud, Philip and Bax, Ad
- publishing date
- 2019-09-04
- type
- Contribution to journal
- publication status
- published
- in
- Journal of the American Chemical Society
- volume
- 141
- issue
- 35
- pages
- 13762 - 13766
- publisher
- The American Chemical Society (ACS)
- external identifiers
-
- scopus:85071788460
- ISSN
- 1520-5126
- DOI
- 10.1021/jacs.9b06970
- language
- English
- LU publication?
- no
- id
- 5ac08dbe-5865-4322-bb1d-a91af8101d1c
- date added to LUP
- 2024-01-25 13:26:21
- date last changed
- 2024-01-29 10:10:29
@article{5ac08dbe-5865-4322-bb1d-a91af8101d1c, abstract = {{Brain tissue of Alzheimer’s disease patients invariably contains deposits of insoluble, fibrillar aggregates of peptide fragments of the amyloid precursor protein (APP), typically 40 or 42 residues in length and referred to as Aβ40 and Aβ42. However, it remains unclear whether these fibrils or oligomers constitute the toxic species. Depending on sample conditions, oligomers can form in a few seconds or less. These oligomers are invisible to solution NMR spectroscopy, but they can be rapidly (<1 s) resolubilized and converted to their NMR-visible monomeric constituents by raising the hydrostatic pressure to a few kbar. Hence, utilizing pressure-jump NMR, the oligomeric state can be studied at residue-specific resolution by monitoring its signals in the monomeric state. Oligomeric states of Aβ40 exhibit a high degree of order, reflected by slow longitudinal 15N relaxation (T1 > 5 s) for residues 18–21 and 31–34, whereas the N-terminal 10 residues relax much faster (T1 ≤ 1.5 s), indicative of extensive internal motions. Transverse relaxation rates rapidly increase to ca. 1000 s–1 after the oligomerization is initiated.}}, author = {{Barnes, C. Ashley and Robertson, Angus J. and Louis, John M. and Anfinrud, Philip and Bax, Ad}}, issn = {{1520-5126}}, language = {{eng}}, month = {{09}}, number = {{35}}, pages = {{13762--13766}}, publisher = {{The American Chemical Society (ACS)}}, series = {{Journal of the American Chemical Society}}, title = {{Observation of β-Amyloid Peptide Oligomerization by Pressure-Jump NMR Spectroscopy}}, url = {{http://dx.doi.org/10.1021/jacs.9b06970}}, doi = {{10.1021/jacs.9b06970}}, volume = {{141}}, year = {{2019}}, }