Zinc(II) modulates specifically amyloid formation and structure in model peptides

被引:24
作者
Alies, Bruno [1 ,2 ]
Pradines, Vincent [1 ,2 ]
Llorens-Alliot, Isabelle [3 ]
Sayen, Stephanie [4 ]
Guillon, Emmanuel [4 ]
Hureau, Christelle [1 ,2 ]
Faller, Peter [1 ,2 ]
机构
[1] CNRS, Chim Coordinat Lab, F-31077 Toulouse, France
[2] Univ Toulouse, UPS, INPT, F-31077 Toulouse, France
[3] CEA DSM INAC NRS, F-38000 Grenoble, France
[4] Univ Reims, Grp Chim Coordinat, CNRS, ICMR,UMR 6229, F-51687 Reims 2, France
来源
JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY | 2011年 / 16卷 / 02期
关键词
Amyloid; Zinc; Copper; Aggregation; Spectroscopy; PROTEIN AGGREGATION; ALZHEIMERS-DISEASE; METAL-BINDING; BETA PEPTIDE; COORDINATION; IONS; CU(II); COPPER; OLIGOMERIZATION; ZN(II);
D O I
10.1007/s00775-010-0729-8
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
Metal ions such as zinc and copper can have dramatic effects on the aggregation kinetics of and the structures formed by several amyloidogenic peptides/proteins. Depending on the identity of the amyloidogenic peptide/protein and the conditions, Zn(II) and Cu(II) can promote or inhibit fibril formation, and in some cases these metal ions have opposite effects. To better understand this modulation of peptide aggregation by metal ions, the impact of Zn(II) binding to three amyloidogenic peptides (A beta 14-23, A beta 11-23, and A beta 11-28) on the formation and structure of amyloid-type fibrils was investigated. Zn(II) was able to accelerate fibril formation for all three peptides as measured by thioflavin T fluorescence and transmission electron microscopy. The effects of Zn(II) on A beta 11-23 and A beta 11-28 aggregation were very different compared with the effects of Cu(II), showing that these promoting effects were metal-specific. X-ray absorption spectroscopy suggested that the Zn(II) binding to A beta 11-23 and A beta 11-28 is very different from Cu(II) binding, but that the binding is similar in the case of A beta 14-23. A model is proposed in which the different coordination chemistry of Zn(II) compared with Cu(II) explains the metal-specific effect on aggregation and the difference between peptides A beta 14-23 and A beta 11-23/A beta 11-28.
引用
收藏
页码:333 / 340
页数:8
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