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Phosphorylation modifies the molecular stability of ?-amyloid deposits.

ABSTRACT: Protein aggregation plays a crucial role in neurodegenerative diseases. A key feature of protein aggregates is their ubiquitous modification by phosphorylation. Little is known, however, about the molecular consequences of phosphorylation of protein aggregates. Here we show that phosphorylation of ?-amyloid at serine 8 increases the stability of its pathogenic aggregates against high-pressure and SDS-induced dissociation. We further demonstrate that phosphorylation results in an elevated number of hydrogen bonds at the N terminus of ?-amyloid, the region that is critically regulated by a variety of post-translational modifications. Because of the increased lifetime of phosphorylated ?-amyloid aggregates, phosphorylation can promote the spreading of ?-amyloid in Alzheimer pathogenesis. Our study suggests that regulation of the molecular stability of protein aggregates by post-translational modifications is a crucial factor for disease progression in the brain.

SUBMITTER: Rezaei-Ghaleh N

PROVIDER: S-EPMC4833870 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Phosphorylation modifies the molecular stability of β-amyloid deposits.

Rezaei-Ghaleh Nasrollah N Amininasab Mehriar M Kumar Sathish S Walter Jochen J Zweckstetter Markus M

Nature communications 20160413

Protein aggregation plays a crucial role in neurodegenerative diseases. A key feature of protein aggregates is their ubiquitous modification by phosphorylation. Little is known, however, about the molecular consequences of phosphorylation of protein aggregates. Here we show that phosphorylation of β-amyloid at serine 8 increases the stability of its pathogenic aggregates against high-pressure and SDS-induced dissociation. We further demonstrate that phosphorylation results in an elevated number ...[more]

PMID: 27072999

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