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J Pept Sci. 2017 Nov;23(11):810-817. doi: 10.1002/psc.3028. Epub 2017 Aug 10.

Dissecting the behaviour of β-amyloid peptide variants during oligomerization and fibrillation.

Author information

1
Research Institute of Atherosclerotic Disease, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an, 710061, China.
2
School of Medicine, Xizang Minzu University, Xianyang, 712082, China.
3
Department of Biochemistry and Molecular Biology, Xi'an Jiaotong University, Xi'an, 710061, China.

Abstract

The oligomerization and fibrillation of β-amyloid (Aβ) peptides are important events in the pathogenesis of Alzheimer's disease. However, the motifs within the Aβ sequence that contribute to oligomerization and fibrillation and the complex interplay among these short motifs are unclear. In this study, the oligomerization and fibrillation abilities of the Aβ variants Aβ1-28, Aβ1-36, Aβ11-42, Aβ17-42, Aβ1-40 and Aβ1-42 were examined by thioflavin T fluorescence, western blotting and transmission electron microscopy. Compared with two C-terminal-truncated peptides (i.e. Aβ1-28 and Aβ1-36), Aβ11-42, Aβ17-42 and Aβ1-42 had stronger abilities to form oligomers. This indicated that amino acids 37-42 strengthen the β-hairpin structure of Aβ. Both Aβ1-42 and Aβ1-40 could form fibres, but Aβ17-42 formed irregular fibres, suggesting that amino acids 1-17 were essential for Aβ fibre formation. Aβ1-28 and Aβ1-36 exhibited weak oligomerization and fibrillation, implying that they formed an unstable β-hairpin structure owing to the incomplete C-terminal region. Intermediate peptides were likely to form a stable structure, consistent with previous results. This work explains the roles and interplay among motifs within Aβ during oligomerization and fibrillation.

KEYWORDS:

fibrillation; motif; oligomerization; β-amyloid peptide

PMID:
28795459
DOI:
10.1002/psc.3028
[Indexed for MEDLINE]

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