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Distinct Effects of O‐GlcNAcylation and Phosphorylation of a Tau‐Derived Amyloid Peptide on Aggregation of the Native Peptide
Author(s) -
FrenkelPinter Moran,
Richman Michal,
Belostozky Anna,
AbuMokh Amjaad,
Gazit Ehud,
Rahimipour Shai,
Segal Daniel
Publication year - 2018
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201802209
Subject(s) - peptide , phosphorylation , chemistry , glycan , amyloid (mycology) , biochemistry , protein aggregation , protein folding , p3 peptide , biophysics , amyloid precursor protein , biology , alzheimer's disease , glycoprotein , medicine , inorganic chemistry , disease , pathology
Protein phosphorylation and O‐GlcNAcylation are very common nucleoplasmic post‐translational modifications. Mono‐addition of either the phosphate or the O‐GlcNAc group were shown to inhibit the self‐aggregation of amyloidogenic proteins and peptides, which is the hallmark of various protein misfolding diseases. However, their comparable effect upon co‐incubation with a native non‐modified amyloid scaffold has not been reported. O‐linked glycans and phosphate variants of the tau protein‐derived VQIVYK hexapeptide motif were generated as a simplified amyloid scaffold model and demonstrate that, while self‐aggregation can be attenuated by either a single glycan or a phosphate unit, only co‐incubation with the O‐GlcNAc variant inhibits aggregation of the native peptide. These results shed light on the role of post‐translational modifications in protein aggregation and suggest a novel therapeutic approach to protein misfolding diseases.