Position-selective glycosylation tempers aggregation propensity

Our recent paper in Science Advances investigates the impact of posttranslational modifications (PTMs) on aggregation-prone regions (APRs).

Employing proteome-wide computational analyses and biophysical techniques, we uncovered a unique enrichment of N-glycosylation flanking APRs, thereby often replacing unmodified aggregation gatekeeper residues at these positions, suggesting an evolutionarily selected role in preventing misfolding. Our experimental evidence furthermore demonstrates that N-glycosylation acts as a potent inhibitor of peptide aggregation. Intriguingly, mining proteomics data reveals a direct link between the loss of N-glycans at APR flanks and protein aggregation in cellular models.

This study highlights another aspect of the multifaceted molecular function of N-glycosylation, emphasizing its pivotal role in averting protein aggregation in higher eukaryotes, and shows the intricate interplay of PTMs and protein aggregation dynamics.

Read the full story here. https://www.science.org/doi/10.1126/sciadv.adk8173