The effect of Aβ conformation on the metal affinity and aggregation mechanism studied by circular dichroism spectroscopy

被引：47
|
作者：
Chen, Y. R.
Huang, H. B.
Chyan, C. L.
Shiao, M. S.
Lin, T. H. [1 ]
Chen, Y. C.
机构：
[1] Tzu Chi Univ, Dept Med Technol, Inst Med Sci, Iwaki, Fukushima 970, Japan
[2] Natl Chung Cheng Univ, Inst Mol Biol, Chiayi 62117, Taiwan
[3] Natl Duan Hwa Univ, Dept Chem, Hualien, Taiwan
[4] Taipei Vet Gen Hosp, Dept Med Res & Educ, Taipei, Taiwan
[5] Natl Yang Ming Univ, Inst Biochem, Taipei 112, Taiwan
[6] Natl Yang Ming Univ, Ins Bioinformat, Taipei 112, Taiwan
[7] Natl Yang Ming Univ, Struct Biol Program, Taipei 112, Taiwan
[8] Tzu Chi Univ, Dept Med Technol, Hualien, Taiwan
来源：
JOURNAL OF BIOCHEMISTRY | 2006年 / 139卷 / 04期
关键词：
Alzheimer's disease; beta-amyloid (A beta); conformational transition; circular dichroism spectroscopy;
D O I：
10.1093/jb/mvj083
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
The conformational change and associated aggregation of beta amyloid (A beta) with or without metals is the main cause of Alzheimers'disease (AD). In order to further understand the effects of A beta and its associated metals on the aggregation mechanism, the influence of A beta conformation on the metal affinity and aggregation was investigated using circular dichroism (CD) spectroscopy. The A beta conformation is dependent on pH and trifluoroethanol (TFE). The binding of metals to A beta was found to be dependent on the A beta conformation. The aggregation induced by A beta itself or its associated metals is completely diminished for A beta in 40% TFE. Only in 5% and 25% TFE can A beta undergo an alpha-helix to beta-sheet aggregation, which involve a three-state mechanism for the metal-free state, and a two-state transition for the metal-bound state, respectively. The aggregation-inducing activity of metals is in the order, Cu2+ > Fe3+ >= Al3+ > Zn2+.
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页码：733 / 740
页数：8
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