Zinc(II) modulates specifically amyloid formation and structure in model peptides
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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 (Aβ14-23, Aβ11-23, and Aβ11-28) 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 Aβ11-23 and Aβ11-28 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 Aβ11-23 and Aβ11-28 is very different from Cu(II) binding, but that the binding is similar in the case of Aβ14-23. 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 Aβ14-23 and Aβ11-23/Aβ11-28.
KeywordsAmyloid Zinc Copper Aggregation Spectroscopy
European Synchrotron Radiation Facility
Extended X-ray absorption fine structure
Piperazine-1,4-bis-(2-hydroxy-propane-sulfonic acid) dihydrate
X-ray absorption spectroscopy
We acknowledge the ESRF for beamtime provision and the team of beamline FAME 30B, especially Olivier Proux, for their helpful support. We also thank Thomas Lunardi and the EMBL laboratory (Grenoble) for their support in performing UV–vis spectroscopy near the beamline, and Vincent Colliere and Diana Ciuculescu (LCC Toulouse) for part of the transmission electron microscopy experiments. This work was supported by the ESRF (Experiment CH-3015), a grant from the French Ministry (MERT) (B.A.), and a grant from the Agence Nationale de la Recherche (ANR) Programme Blanc NT09-488591, “NEUROMETALS” (P.F. and C.H.).
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