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Identifying Terminal Assembly Propensity of Amyloidal Peptides by Scanning Tunneling Microscopy
Author(s) -
Zheng Yongfang,
Xu Meng,
Yu Lanlan,
Qu Fuyang,
Lin Yuchen,
Xu Jing,
Zou Yimin,
Yang Yanlian,
Wang Chen
Publication year - 2019
Publication title -
chemphyschem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.016
H-Index - 140
eISSN - 1439-7641
pISSN - 1439-4235
DOI - 10.1002/cphc.201800975
Subject(s) - cleavage (geology) , scanning tunneling microscope , highly oriented pyrolytic graphite , peptide , chemistry , biophysics , stereochemistry , n terminus , c terminus , crystallography , peptide sequence , biochemistry , biology , nanotechnology , materials science , amino acid , gene , paleontology , fracture (geology)
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.