Turn Plasticity Distinguishes Different Modes of Amyloid-beta Aggregation
2014 | journal article. A publication with affiliation to the University of Göttingen.
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Turn Plasticity Distinguishes Different Modes of Amyloid-beta Aggregation
Rezaei-Ghaleh, N.; Amininasab, M.; Giller, K.; Kumar, S.; Stuendl, A.; Schneider, A. & Becker, S. et al. (2014)
Journal of the American Chemical Society, 136(13) pp. 4913-4919. DOI: https://doi.org/10.1021/ja411707y
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- Authors
- Rezaei-Ghaleh, Nasrollah; Amininasab, Mehriar; Giller, Karin; Kumar, Sathish; Stuendl, Anne; Schneider, Anja; Becker, Stefan; Walter, Jochen; Zweckstetter, Markus
- Abstract
- Pathogenesis of Alzheimer's disease (AD) is associated with aggregation of the amyloid-beta (A beta) peptide into oligomeric and fibrillar assemblies; however, little is known about the molecular basis of aggregation of A beta into distinct assembly states. Here we demonstrate that phosphorylation at serine 26 (S26) impairs A beta fibrillization while stabilizing its monomers and nontoxic soluble assemblies of nonfibrillar morphology. NMR spectroscopy and replica-exchange molecular dynamics indicate that introduction of a phosphate group or phosphomimetic at position 26 diminishes A beta's propensity to form a beta-hairpin, rigidifies the region around the modification site, and interferes with formation of a fibril-specific salt bridge between aspartic acid 23 and lysine 28. The combined data demonstrate that phosphorylation of S26 prevents a distinct conformational rearrangement that is required for progression of A beta aggregation toward fibrils and provide a basis for a possible role of phosphorylation at serine 26 in AD.
- Issue Date
- 2014
- Status
- published
- Publisher
- Amer Chemical Soc
- Journal
- Journal of the American Chemical Society
- ISSN
- 0002-7863
- Sponsor
- DFG [ZW 71/2-2, ZW 71/3-2, WA1477/6-2]