Rezaei-Ghaleh, Nasrollah

[["dc.bibliographiccitation.firstpage","4913"],["dc.bibliographiccitation.issue","13"],["dc.bibliographiccitation.journal","Journal of the American Chemical Society"],["dc.bibliographiccitation.lastpage","4919"],["dc.bibliographiccitation.volume","136"],["dc.contributor.author","Rezaei-Ghaleh, Nasrollah"],["dc.contributor.author","Amininasab, Mehriar"],["dc.contributor.author","Giller, Karin"],["dc.contributor.author","Kumar, Sathish"],["dc.contributor.author","Stuendl, Anne"],["dc.contributor.author","Schneider, Anja"],["dc.contributor.author","Becker, Stefan"],["dc.contributor.author","Walter, Jochen"],["dc.contributor.author","Zweckstetter, Markus"],["dc.date.accessioned","2018-11-07T09:41:25Z"],["dc.date.available","2018-11-07T09:41:25Z"],["dc.date.issued","2014"],["dc.description.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."],["dc.description.sponsorship","DFG [ZW 71/2-2, ZW 71/3-2, WA1477/6-2]"],["dc.identifier.doi","10.1021/ja411707y"],["dc.identifier.isi","000333947900030"],["dc.identifier.pmid","24617810"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/33723"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Chemical Soc"],["dc.relation.issn","0002-7863"],["dc.title","Turn Plasticity Distinguishes Different Modes of Amyloid-beta Aggregation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","16059"],["dc.bibliographiccitation.issue","31"],["dc.bibliographiccitation.journal","Journal of Biological Chemistry"],["dc.bibliographiccitation.lastpage","16067"],["dc.bibliographiccitation.volume","291"],["dc.contributor.author","Rezaei-Ghaleh, Nasrollah"],["dc.contributor.author","Kumar, Sathish"],["dc.contributor.author","Walter, Jochen"],["dc.contributor.author","Zweckstetter, Markus"],["dc.date.accessioned","2020-12-10T18:12:56Z"],["dc.date.available","2020-12-10T18:12:56Z"],["dc.date.issued","2016"],["dc.description.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-beta (A beta) peptide and investigate how phosphorylation at serine 8 affects the structure of A beta aggregates. Serine 8 is shown to be located in a region of high conformational flexibility in monomeric A beta, which upon phosphorylation undergoes changes in local conformational dynamics. Using hydrogen-deuterium exchange NMR and fluorescence quenching techniques, we demonstrate that A beta phosphorylation at serine 8 causes structural changes in the N-terminal region of A beta 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 A beta aggregates. Our data therefore support an important role of posttranslational modifications in the structural polymorphism of amyloid aggregates and their modulatory effect on neurodegeneration."],["dc.identifier.doi","10.1074/jbc.M116.728956"],["dc.identifier.eissn","1083-351X"],["dc.identifier.isi","000380585400012"],["dc.identifier.issn","0021-9258"],["dc.identifier.pmid","27252381"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/74537"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Soc Biochemistry Molecular Biology Inc"],["dc.relation.issn","1083-351X"],["dc.relation.issn","0021-9258"],["dc.title","Phosphorylation Interferes with Maturation of Amyloid-β Fibrillar Structure in the N Terminus"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]