Elucidating the Unique J-Shaped Protomer Structure of Amyloid-β(1-40) Fibril with Cryo-Electron Microscopy.

ABSTRACT: Although the structural diversity of amyloid-β (Aβ) fibrils plays a critical role in the pathology of Alzheimer's disease (AD), the mechanisms underlying this diversity remain poorly understood. In this study, we report the discovery of a novel J-shaped protomer structure of Aβ40 fibrils, resolved at 3.3 Å resolution using cryo-electron microscopy. Under controlled conditions (20 mM sodium phosphate buffer, pH 8.0) designed to emphasize intra-protomer interactions and slow fibril elongation, the J-shaped structure revealed distinct salt bridges (e.g., D1-K28, R5-E22) that stabilize the fibril core. These findings expand our understanding of the free energy landscape of fibril formation, shedding light on how specific environmental factors, such as pH and ionic strength, may influence fibri

SUBMITTER: Burton-Smith RN 

PROVIDER: S-EPMC11817843 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature