Tyrosine O-GalNAc Alters the Conformation and Proteolytic Susceptibility of APP Model Glycopeptides.

ABSTRACT: The amyloid-β precursor protein (APP) undergoes proteolytic cleavage by α-, β-, and γ-secretases, to determine its fate in Alzheimer's disease (AD) pathogenesis. Recent findings suggest a possible role of O-glycosylation in APP's proteolytic processing. Therefore, we synthesized native and Swedish-double-mutated APP (glyco)peptides with Tyr⁶⁸¹-O-GalNAc. We studied conformational changes and proteolytic processing using circular dichroism (CD) spectroscopy and enzyme cleavage assay, respectively. CD analysis was carried out in four solvent systems to evaluate peptide environment and O-glycosylation induced conformational changes. The Swedish mutation and Tyr⁶⁸¹-O-GalNAc were the key factors driving conformational changes. Furthermore, the le

SUBMITTER: Singh Y 

PROVIDER: S-EPMC8378340 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature