An O-glycopeptide participates in the formation of distinct Aβ₄₂ fibril structures and attenuates Aβ₄₂ neurotoxicity.

ABSTRACT: The self-assembly of biomolecules through noncovalent interactions is critical in both physiological and pathological processes, as exemplified by the assembly of amyloid β peptide (Aβ) into oligomers or fibrils in Alzheimer's disease (AD). Developing molecules that can modulate this assembly process holds significant mechanistic and therapeutic potential. In this study, we identified glycopeptides as a class of protein aggregation modulators, showing that β-N-acetylgalactosamine (β-GalNAc)-modified Aβ_9-21 promotes Aβ₄₂ fibrillation while reducing its toxic oligomers. Using biochemical assays, cryo-EM, and molecular dynamics simulations, we demonstrated that β-GalNAc-modified Aβ_9-21 coassembles with Aβ₄₂, forming unique fibril structures stabiliz

SUBMITTER: Wei Q 

PROVIDER: S-EPMC12214615 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature