Effect of Cross-Seeding of Wild-Type Amyloid-β_1-40 Peptides with Post-translationally Modified Fibrils on Internal Dynamics of the Fibrils Using Deuterium Solid-State NMR.

ABSTRACT: Post-translationally modified (PTM) amyloid-β (Aβ) species can play an important role in modulating Alzheimer's disease pathology. These relatively less populated modifications can cross-seed the wild-type Aβ peptides to produce fibrils that retain many structural and functional features of the original PTM variants. We focus on studies of internal flexibility in the cross-seeded Aβ_1-40 fibrils originating from seeding with two PTM variants with modifications in the disordered N-terminal domain: ΔE3 truncation and S8-phosphorylation. We employ an array of ²H solid-state NMR techniques, including line shape analysis over a broad temperature range, longitudinal relaxation, and quadrupolar CPMG, to assess the dynamics of the cross-seeded fibrils. The focus is plac

SUBMITTER: Rodgers A 

PROVIDER: S-EPMC10257444 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature