L17A/F19A Substitutions Augment the α-Helicity of β-Amyloid Peptide Discordant Segment.

• Published in: PLOS ONE
• Main Authors: Chu-Ting Liang, Hsien-Bin Huang, Chih-Ching Wang, Yi-Ru Chen, Chi-Fon Chang, Ming-Shi Shiao, Yi-Cheng Chen, Ta-Hsien Lin
• Format: Article in Journal/Newspaper
• Language: English
• Published: Public Library of Science (PLoS) 2016
• Subjects: Medicine; R; Science; Q; Arctic
• Online Access: https://doi.org/10.1371/journal.pone.0154327; https://doaj.org/article/b7c44c3f74f54977bae6babf14526c7f

β-amyloid peptide (Aβ) aggregation has been thought to be associated with the pathogenesis of Alzheimer's disease. Recently, we showed that L17A/F19A substitutions may increase the structural stability of wild-type and Arctic-type Aβ40 and decrease the rates of structural conversion and fibril formation. However, the underlying mechanism for the increase of structural stability as a result of the alanine substitutions remained elusive. In this study, we apply nuclear magnetic resonance and circular dichroism spectroscopies to characterize the Aβ40 structure, demonstrating that L17A/F19A substitutions can augment the α-helicity of the residues located in the α/β-discordant segment (resides 15 to 23) of both wild-type and Arctic-type Aβ40. These results provide a structural basis to link the α-helicity of the α/β-discordant segment with the conformational conversion propensity of Aβ.