L17A/F19A substitutions augment the α-helicity of β-amyloid peptide discordant segment

Chu Ting Liang; Hsien Bin Huang; Chih Ching Wang; Yi Ru Chen; Chi Fon Chang; Ming Shi Shiao; Yi G. Chen; Ta Hsien Lin

doi:10.1371/journal.pone.0154327

L17A/F19A substitutions augment the α-helicity of β-amyloid peptide discordant segment

Chu Ting Liang, Hsien Bin Huang, Chih Ching Wang, Yi Ru Chen, Chi Fon Chang^*, Ming Shi Shiao, Yi G. Chen, Ta Hsien Lin

^*Corresponding author for this work

Department of Biochemistry

Research output: Contribution to journal › Article › peer-review

7 Scopus citations

Abstract

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.

Original language	English
Article number	e0154327
Journal	PLoS ONE
Volume	11
Issue number	4
DOIs	https://doi.org/10.1371/journal.pone.0154327
State	Published - Apr 2016

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title = "L17A/F19A substitutions augment the α-helicity of β-amyloid peptide discordant segment",

abstract = "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.",

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AU - Liang, Chu Ting

AU - Huang, Hsien Bin

AU - Wang, Chih Ching

AU - Chen, Yi Ru

AU - Chang, Chi Fon

AU - Shiao, Ming Shi

AU - Chen, Yi G.

AU - Lin, Ta Hsien

N1 - Publisher Copyright: © 2016 Liang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

PY - 2016/4

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N2 - 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.

AB - 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.

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L17A/F19A substitutions augment the α-helicity of β-amyloid peptide discordant segment

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