Distinct Effects of O‐GlcNAcylation and Phosphorylation of a Tau‐Derived Amyloid Peptide on Aggregation of the Native Peptide. Issue 53 (24th August 2018)

• Record Type: Journal Article
• Authors: Frenkel‐Pinter, Moran; Richman, Michal; Belostozky, Anna; Abu‐Mokh, Amjaad; Gazit, Ehud; Rahimipour, Shai; Segal, Daniel
• Is Part Of: Chemistry. Volume 24:Issue 53(2018)
• Page Start: 14039
• Page End: 14043
• Publication Date: 2018-08-24
• Subjects: aggregation -- amyloid formation -- glycosylation -- peptides -- phosphorylation -- protein folding; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.201802209
• Languages: English
• ISSNs: 0947-6539

Abstract

Abstract: 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. Abstract : Phosphorylation and O‐GlcNAcylation of proteins play a pivotal role in misfolding and aggregation, which are the hallmarks of many amyloidogenic diseases. It was found that, whereas both glycosylation and phosphorylation of a tau‐derived peptide (11aa) inhibited its aggregation, only the glycosylated variant reduced the aggregation of PHF6 upon co‐incubation.