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  Phosphorylation interferes with maturation of amyloid-β fibrillar structure in the N terminus.

Rezaei-Ghaleh, N., Kumar, S., Walter, J., & Zweckstetter, M. (2016). Phosphorylation interferes with maturation of amyloid-β fibrillar structure in the N terminus. Journal of Biological Chemistry, 291(31), 16059-16067. doi:10.1074/jbc.M116.728956.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-002B-4245-9 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-002D-58AF-B
Genre: Journal Article

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Rezaei-Ghaleh, N.1, Author              
Kumar, S., Author
Walter, J., Author
Zweckstetter, M.1, Author              
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1Research Group of Protein Strcture Determination using NMR, MPI for biophysical chemistry, Max Planck Society, ou_578571              

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Free keywords: Alzheimer disease; amyloid-β (Aβ); hydrogen-deuterium exchange; nuclear magnetic resonance (NMR); phosphorylation
 Abstract: Neurodegeneration is characterized by the ubiquitous presence of modifications in protein deposits. Despite their potential significance in the initiation and progression of neurodegenerative diseases, the effects of posttranslational modifications on the molecular properties of protein aggregates are largely unknown. Here, we study the Alzheimer disease-related amyloid-β (Aβ) peptide and investigate how phosphorylation at serine 8 affects the structure of Aβ aggregates. Serine 8 is shown to be located in a region of high conformational flexibility in monomeric Aβ, which upon phosphorylation undergoes changes in local conformational dynamics. Using hydrogen-deuterium exchange NMR and fluorescence quenching techniques, we demonstrate that Aβ phosphorylation at serine 8 causes structural changes in the N-terminal region of Aβ aggregates in favor of less compact conformations. Structural changes induced by serine 8 phosphorylation can provide a mechanistic link between phosphorylation and other biological events that involve the N-terminal region of Aβ aggregates. Our data therefore support an important role of posttranslational modifications in the structural polymorphism of amyloid aggregates and their modulatory effect on neurodegeneration.

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Language(s): eng - English
 Dates: 2016-06-012016-07-29
 Publication Status: Published in print
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 Rev. Method: Peer
 Identifiers: DOI: 10.1074/jbc.M116.728956
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Title: Journal of Biological Chemistry
Source Genre: Journal
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Pages: - Volume / Issue: 291 (31) Sequence Number: - Start / End Page: 16059 - 16067 Identifier: -