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Journal of Biochemistry 2006 139(4):733-740; doi:10.1093/jb/mvj083
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© 2006 The Japanese Biochemical Society.

Regular Paper

The Effect of Aß Conformation on the Metal Affinity and Aggregation Mechanism Studied by Circular Dichroism Spectroscopy

Y.R. Chen1, H.B. Huang2, C.L. Chyan3, M.S. Shiao4, T.H. Lin4,5,6,* and Y.C. Chen1,7,*

1 Institute of Medical Science, Tzu Chi University, Hualien, Taiwan; 2 Institute of Molecular Biology, National Chung-Cheng University, Chiayi, Taiwan; 3 Department of Chemistry, National Duan-Hwa University, Hualien, Taiwan; 4 Department of Medical Research and Education, Taipei Veterans General Hospital, Shihpai, Taipei, Taiwan; 5 Institute of Biochemistry and 6 Institute of Bioinformatics and Structural Biology Program, National Yang-Ming University, Shihpai, Taipei, Taiwan; and 7 Department of Medical Technology, Tzu Chi University, Hualien, Taiwan

* To whom correspondence should be addressed at: Department of Medical Technology, Tzu Chi University, Hualien 970, Taiwan. Fax: +886-3-8571917, E-mail: chen15{at}mail.tcu.edu.tw (Y.C. Chen); Department of Medical Research & Education, Taipei Veterans General Hospital, Teipei, Taiwan. E-mail: thlin@vghtpe.gov.tw (T.H. Lin).

The conformational change and associated aggregation of ß amyloid (Aß) with or without metals is the main cause of Alzheimers' disease (AD). In order to further understand the effects of Aß and its associated metals on the aggregation mechanism, the influence of Aß conformation on the metal affinity and aggregation was investigated using circular dichroism (CD) spectroscopy. The Aß conformation is dependent on pH and trifluoroethanol (TFE). The binding of metals to Aß was found to be dependent on the Aß conformation. The aggregation induced by Aß itself or its associated metals is completely diminished for Aß in 40% TFE. Only in 5% and 25% TFE can Aß undergo an {alpha}-helix to ß-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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