A Hairpin Motif in the Amyloid-β Peptide Is Important for Formation of Disease-Related Oligomers.

ABSTRACT: The amyloid-β (Aβ) peptide is associated with the development of Alzheimer's disease and is known to form highly neurotoxic prefibrillar oligomeric aggregates, which are difficult to study due to their transient, low-abundance, and heterogeneous nature. To obtain high-resolution information about oligomer structure and dynamics as well as relative populations of assembly states, we here employ a combination of native ion mobility mass spectrometry and molecular dynamics simulations. We find that the formation of Aβ oligomers is dependent on the presence of a specific β-hairpin motif in the peptide sequence. Oligomers initially grow spherically but start to form extended linear aggregates at oligomeric states larger than those of the tetramer. The population of the extended oligomers could

SUBMITTER: Khaled M 

PROVIDER: S-EPMC10450692 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature