Aggregation and Fibril Structure of AβM01-42 and Aβ1-42

摘要: A mechanistic understanding of Aβ aggregation and high-resolution structures fibrils oligomers are vital to elucidating relevant details neurodegeneration in Alzheimer's disease, which will facilitate the rational design diagnostic therapeutic protocols. The most detailed reproducible insights into structure kinetics have been achieved using peptides produced by recombinant expression, results an additional methionine at N-terminus. While length C-terminus is well established a profound impact on peptide's propensity, structure, neurotoxicity, N-terminal pathways unclear. For this reason, we developed protocol produce Aβ1-42, sans methionine, small ubiquitin-like modifier-Aβ1-42 fusion protein reasonable yield, with compared AβM01-42 containing residue. data revealed that Aβ1-42 aggregate similar rates same mechanism, generation new aggregates dominated secondary nucleation monomers surface fibrils. We also recorded magic angle spinning nuclear magnetic resonance spectra demonstrated excellent spectral resolution maintained both chemical shifts virtually identical dipolar recoupling experiments provide information about rigid residues. Collectively, these indicate fibril core unaffected methionine. This consistent recent M0 located terminus disordered 14-amino acid tail.