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+.

引用

页码：733 / 740

页数：8

共 46 条

[1] Dramatic aggregation of Alzheimer Aβ by Cu(II) is induced by conditions representing physiological acidosis [J].