Identifying Terminal Assembly Propensity of Amyloidal Peptides by Scanning Tunneling Microscopy. Issue 1 (5th December 2018)

• Record Type: Journal Article
• Authors: Zheng, Yongfang; Xu, Meng; Yu, Lanlan; Qu, Fuyang; Lin, Yuchen; Xu, Jing; Zou, Yimin; Yang, Yanlian; Wang, Chen
• Is Part Of: Chemphyschem. Volume 20:Issue 1(2019)
• Page Start: 103
• Page End: 107
• Publication Date: 2018-12-05
• Subjects: assembly -- beta-amyloids -- N-terminally extended beta-amyloids -- peptides -- scanning tunneling microscopy; Chemistry, Physical and theoretical -- Periodicals; 541.05
• DOI: 10.1002/cphc.201800975
• Languages: English
• ISSNs: 1439-4235

Abstract

Abstract: The abnormal accumulation of beta‐amyloids (Aβ) in brain is considered as a key initiating cause for Alzheimer's disease (AD) due to their richness in plaques and self‐aggregate propensity. In recent studies, N‐terminally extended Aβ peptides (NTE‐Aβ) with the N‐terminus originating prior to the canonical β‐secretase cleavage site were found in humans and suggested to have possible relevance to AD. However, the effects of the extended N‐terminus on the amyloidegenic structure and aggregation propensity have not been fully elucidated. Herein, we characterized the assembly structures of Aβ1‐42, Aβ(−5)‐42, Aβ(−10)–42 and Aβ(−15)‐42 with both normal and reversed sequences on highly oriented pyrolytic graphite (HOPG) surfaces with scanning tunneling microscopy (STM). The molecularly resolved surface‐mediated peptide assemblies enable identification of amyloidegenic fragments. The observations reveal that the assembly propensity of the C‐terminal strand of Aβ1‐42 is highly conserved and insensitive to N‐terminal extensions. In contrast, different assembly structures of the N‐terminal strand of Aβ variants can be observed with possible assignment of varied amyloidegenic fragments in the extended N‐termini, which may contribute to the varied aggregation propensities of Aβ42 species. Abstract : Terminal destabilization : The C‐terminal strand of Aβ1‐42 starts from Ala30 and the N‐terminal folding site is observed to be Glu22. N‐terminal extensions with possible assignment of varied amyloidegenic fragments exert great destabilization effects on the surface‐mediated assembly of N‐terminal β‐strand of Aβ1‐42. In contrast, C‐terminal strand is highly conserved and insensitive to the extensions.