Mechanism of zinc(II)-promoted amyloid formation: zinc(II) binding facilitates the transition from the partially α-helical conformer to aggregates of amyloid β protein(1–28)

  • Christine Talmard
  • Rodrigue Leuma Yona
  • Peter FallerEmail author
Original Paper


The amyloidoses are a group of disorders characterized by aberrant protein folding and assembly, leading to the deposition of insoluble protein fibrils (amyloid), which provokes cell dysfunction and later cell death. One of the physiologically relevant environmental factors able to affect the conformation and hence the aggregation properties of amyloidogenic proteins/peptides is metal ions. Zn(II) promotes aggregation of most amyloidogenic peptides/proteins in vitro, including amyloid β protein (Aβ), but the underlying mechanism is not known. To better understand this mechanism the present study focused on the partially α-helical conformer, supposed to be an intermediate in Aβ aggregation. This partially α-helical conformer is stabilized by 10–20% 2,2,2-trifluoroethanol (TFE): therefore, the influence of Zn binding on the aggregation of the amylidogenic model peptide Aβ(1–28) (Aβ28) was investigated at different TFE concentrations. The results showed a synergistic effect of Zn(II) and 10% TFE, i.e., that either Zn or 10% TFE accelerated Aβ28 aggregation on its own, but with them together an at least 10 times promotion of Aβ28 aggregation was observed. Further studies by thioflavin T fluorescence spectroscopy, transmission electron microscopy, and circular dichroism (CD) spectroscopy suggested that the aggregates of Zn-Aβ28 formed in 10%TFE contain a β-sheet secondary structure and are more of the amyloid type. CD spectroscopy indicated that Zn binding disrupted partially the α-helical structure of Aβ28 in TFE. Thus, we propose that the promotion of Aβ28 aggregation by Zn is based on the transformation of the partially α-helical conformer (intermediate) towards the β-sheet amyloid structure by a destabilization of the α-helix in the intermediate.


Amyloid β protein Zinc Peptide structure Aggregation 


Amyloid β protein


Amyloid β protein(1–16)


Amyloid β protein(1–28)


Amyloid β protein(1–40)


Circular dichroism


4-(2-Hydroxyethyl)-1-piperazineethanesulfonic acid


Sodium dodecyl sulfate


Transmission electron microscopy




Thioflavin T



We would like to thank Jade Durand and Vincent Colliere for sample preparation for TEM and the TEM measurements, respectively. This work was supported by a grant from the French ministry, ACI-INTERFACE PCB (DRAB), and the University Paul Sabatier (BQR ASUPS AO3). C.T. was supported by a grant from ESF and R.L.Y. by a grant from the Association France Alzheimer.

Supplementary material

775_2008_461_MOESM1_ESM.doc (128 kb)
Supplementary figures (DOC 129 kb)


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Copyright information

© SBIC 2008

Authors and Affiliations

  • Christine Talmard
    • 1
    • 2
  • Rodrigue Leuma Yona
    • 1
    • 2
  • Peter Faller
    • 1
    • 2
    Email author
  1. 1.LCC (Laboratoire de Chimie de Coordination)CNRSToulouseFrance
  2. 2.UPS, INPT, LCCUniversité de ToulouseToulouseFrance

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