Abstract
The 14-3-3 proteins are a highly conserved adaptor protein family with multi-layer functions, abundantly expressed in the brain. The 14-3-3 proteins modulate phosphorylation, regulate enzymatic activity and can act as chaperones. Most importantly, they play an important role in various neurodegenerative disorders due to their vast interaction partners. Particularly, the 14-3-3ζ isoform is known to co-localize in aggregation tangles in both Alzheimer's and Parkinson's diseases as a result of protein-protein interactions. These abnormal clumps consist of amyloid fibrils, insoluble aggregates, mainly formed by the amyloid-β, tau and α-synuclein proteins. However, the molecular basis of if and how 14-3-3ζ can aggregate into amyloid fibrils is unknown. In this study, we describe the formation of amyloid fibrils by 14-3-3ζ using a comprehensive approach that combines bioinformatic tools, amyloid-specific dye binding, secondary structure analysis and atomic force microscopy. The results presented herein characterize the amyloidogenic properties of 14-3-3ζ and imply that the well-folded protein undergoes aggregation to β-sheet-rich amyloid fibrils.