1. Monitoring early-stage β-amyloid dimer aggregation by histidine site-specific two-dimensional infrared spectroscopy in a simulation study.
- Author
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Chatterjee S, Nam Y, Salimi A, and Lee JY
- Subjects
- Molecular Dynamics Simulation, Peptide Fragments chemistry, Protein Conformation, beta-Strand, Amyloid beta-Peptides chemistry, Histidine chemistry
- Abstract
Monitoring early-stage β-amyloid (Aβ) dimerization is a formidable challenge for understanding neurological diseases. We compared β-sheet formation and histidine site-specific two-dimensional infrared (2D IR) spectroscopic signatures of Aβ dimers with different histidine states (δ; N
δ1 -H, ε; Nε2 -H, or π; both protonated). Molecular dynamics (MD) simulations revealed that β-sheet formation is favored for the δδδ:δδδ and πππ:πππ tautomeric isomers showing strong couplings and frequent contacts between the central hydrophobic core and C-terminus compared with the εεε:εεε isomer. Characteristic blue-shifts in the 2D IR central bands were observed upon monomer-dimer transformation. The εεε:εεε dimer exhibited larger frequency shifts than δδδ:δδδ and πππ:πππ implying that the red-shift may have a correlation with Nδ1 -H(δ) protonation. Our results support the tautomerization/protonation hypothesis that attributes Aβ misfolding to histidine tautomers as a possible primary initiator for Aβ aggregation and facilitates the application of histidine site-specific 2D IR spectroscopy for studying early-stage Aβ self-assembly.- Published
- 2022
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