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Published on: October 25, 2017
Zinc(II) modulates specifically amyloid formation and structure in model peptides
Bruno Alies1, Vincent Pradines, Isabelle Llorens-Alliot
1LCC (Laboratoire de Chimie de Coordination), CNRS, 205 route de Narbonne, 31077 Toulouse, France.
Summary
Zinc (Zn(II)) and copper (Cu(II)) ions significantly influence amyloid peptide aggregation. This study shows Zn(II) accelerates fibril formation in Aβ peptides, revealing metal-specific effects crucial for understanding amyloid diseases.
Area of Science:
- Biochemistry
- Biophysics
- Materials Science
Background:
- Metal ions like zinc and copper profoundly impact amyloidogenic peptide/protein aggregation kinetics and structures.
- Zn(II) and Cu(II) can either promote or inhibit fibril formation, with effects varying based on the specific peptide and experimental conditions.
- Opposing effects of metal ions on fibril formation highlight the need for detailed investigation into metal-peptide interactions.
Purpose of the Study:
- To investigate the impact of Zn(II) binding on the formation and structure of amyloid-type fibrils using three specific amyloidogenic peptides: Aβ14-23, Aβ11-23, and Aβ11-28.
- To elucidate the metal-specific effects of Zn(II) compared to Cu(II) on peptide aggregation.
- To understand the underlying coordination chemistry driving these metal-specific aggregation differences.
Main Methods:
- Thioflavin T fluorescence assays to monitor fibril formation kinetics.
- Transmission electron microscopy (TEM) to visualize fibril structures.
- X-ray absorption spectroscopy (XAS) to probe the coordination environment of metal ions bound to peptides.
Main Results:
- Zn(II) significantly accelerated fibril formation for all three investigated peptides (Aβ14-23, Aβ11-23, Aβ11-28).
- The aggregation-promoting effects of Zn(II) were distinct from those of Cu(II) for Aβ11-23 and Aβ11-28, indicating metal specificity.
- XAS data suggested different Zn(II) and Cu(II) binding modes for Aβ11-23/Aβ11-28, while binding was similar for Aβ14-23.
Conclusions:
- Zn(II) binding accelerates amyloid-type fibril formation in Aβ14-23, Aβ11-23, and Aβ11-28 peptides.
- The observed aggregation effects are metal-specific, with Zn(II) and Cu(II) exhibiting different impacts on peptide aggregation.
- Differences in Zn(II) and Cu(II) coordination chemistry explain the metal-specific modulation of peptide aggregation and the distinct behaviors observed between Aβ14-23 and Aβ11-23/Aβ11-28.
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