Oligomeric Protein Complexes Formed by Beta Amyloid Peptides and Their Molecular Associates
Journal
Chemistry – A European Journal
Journal Volume
31
Journal Issue
38
ISSN
0947-6539
1521-3765
Date Issued
2025-06-06
Author(s)
Lee, Hsiang‐Ting
Chang, Han‐Wen
Lin, Yeh‐Tung
Huang, Shing‐Jong
Wu, Meng‐Hsin
Tsai, Chang‐Shun
Tu, Ling‐Hsien
Lee, Ming‐Che
Chen, Yun‐Ru
Abstract
The aggregation and dysregulation of β-amyloid (Aβ) peptides are critical factors in the pathogenesis of Alzheimer's disease (AD). This study investigates the use of reverse micelles (RMs) as a nanoscale environment to encapsulate Aβ peptides and explore their interactions with zinc ions (Zn2⁺) and a TDP-43 variant, both of which are important binding partners of Aβ peptides closely associated with neurodegenerative diseases. We demonstrate that RMs stabilize Aβ peptides in their oligomeric form, promoting β-sheet formation and enabling detailed structural studies using solid-state NMR. Our findings reveal that Zn2⁺ induces specific conformational changes in residues E11 and E22 of Aβ oligomers but not E3, and that the TDP-43 variant can form stable protein complex with Aβ40, that persists even after extended incubation and sonication. A systematic comparison of the site-specific 13C chemical shifts of the Aβ40 oligomers modulated by the interactions with Zn2⁺, Aβ42, and a TDP-43 variant, revealed that Aβ40 predominantly adopts a β1-loop-β2 motif. Notably, chemical state changes were mainly observed in the residues within the loop region and the charged residues of the β1 region. In contrast, the hydrophobic residues of the β-sheet regions were structurally unaltered upon protein complex formation.
Subjects
beta-amyloid
protein-protein interaction
reverse micelle
solid-state NMR
Publisher
Wiley
Type
journal article