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Journal Article

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

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Rezaei-Ghaleh,  N.
Research Group of Protein Strcture Determination using NMR, MPI for biophysical chemistry, Max Planck Society;

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Zweckstetter,  M.
Research Group of Protein Strcture Determination using NMR, MPI for biophysical chemistry, Max Planck Society;

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Citation

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.


Cite as: http://hdl.handle.net/11858/00-001M-0000-002B-4245-9
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.