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

Y. R. Chen, H. B. Huang, C. L. Chyan, M. S. Shiao, T. H. Lin*, Y. C. Chen

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

51 Scopus citations

Abstract

The conformational change and associated aggregation of β amyloid (Aβ) with or without metals is the main cause of Alzheimers' disease (AD). In order to further understand the effects of Aβ and its associated metals on the aggregation mechanism, the influence of Aβ conformation on the metal affinity and aggregation was investigated using circular dichroism (CD) spectroscopy. The Aβ conformation is dependent on pH and trifluoroethanol (TFE). The binding of metals to Aβ was found to be dependent on the Aβ conformation. The aggregation induced by Aβ itself or its associated metals is completely diminished for Aβ in 40% TFE. Only in 5% and 25% TFE can Aβ undergo an α-helix to β-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+ ≥ Al 3+ > Zn2+.

Original languageEnglish
Pages (from-to)733-740
Number of pages8
JournalJournal of Biochemistry
Volume139
Issue number4
DOIs
StatePublished - 04 2006
Externally publishedYes

Keywords

  • Alzheimer's disease
  • Circular dichroism spectroscopy
  • Conformational transition
  • β-amyloid (Aβ)

Fingerprint

Dive into the research topics of 'The effect of Aβ conformation on the metal affinity and aggregation mechanism studied by circular dichroism spectroscopy'. Together they form a unique fingerprint.

Cite this