title: Phosphorylation modifies the molecular stability of β-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 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 of hydrogen bonds at the N terminus of β-amyloid, the region that is critically regulated by a variety of post-translational modifications. Because of the increased lifetime of phosphorylated β-amyloid aggregates, phosphorylation can promote the spreading of β-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.
authors.affiliation: German Center for Neurodegenerative Diseases (DZNE), 37075 Göttingen, Germany.
authors.forename: Nasrollah
authors.initials: N
authors.lastname: Rezaei-Ghaleh
authors.affiliation: Department of Cell and Molecular Biology, School of Biology, College of Science, University of Tehran, 1417466191 Tehran, Iran.
authors.forename: Mehriar
authors.initials: M
authors.lastname: Amininasab
authors.affiliation: Department of Neurology, University of Bonn, 53127 Bonn, Germany.
authors.forename: Sathish
authors.initials: S
authors.lastname: Kumar
authors.affiliation: Department of Neurology, University of Bonn, 53127 Bonn, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Walter
authors.affiliation: German Center for Neurodegenerative Diseases (DZNE), 37075 Göttingen, Germany.|Department for NMR-based Structural Biology, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany.|Department of Neurology, University Medical Center Göttingen, University of Göttingen, 37073 Göttingen, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Zweckstetter
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism*; D007700:Kinetics; D010766:Phosphorylation / Q000187:drug effects; D010768:Phosphoserine / Q000378:metabolism; D011312:Pressure; D066329:Protein Aggregates / Q000187:drug effects; D055550:Protein Stability; D012967:Sodium Dodecyl Sulfate / Q000494:pharmacology; D013816:Thermodynamics
chemical_list: D016229:Amyloid beta-Peptides; D066329:Protein Aggregates; D010768:Phosphoserine; D012967:Sodium Dodecyl Sulfate