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Published on: June 14, 2012
Modulating amyloid self-assembly and fibril morphology with Zn(II)
Jijun Dong1, Jacob E Shokes, Robert A Scott
1Center for the Analysis of SupraMolecular Self-assemblies, Department of Chemistry, Emory University, 1521 Dickey Drive, Atlanta, Georgia 30322, USA.
Journal of the American Chemical Society
|March 16, 2006
Summary
Zinc ions (Zn(II)) act as probes for amyloid structure in Abeta peptide segments. Zn2+ specifically controls self-assembly rates and amyloid morphology, influencing fiber formation and ribbon/tube structures.
Area of Science:
- Biochemistry
- Materials Science
- Structural Biology
Background:
- Amyloid structures are associated with various diseases.
- Understanding the self-assembly of amyloid peptides is crucial for developing therapeutic strategies.
- Metal ions can influence peptide aggregation and amyloid formation.
Purpose of the Study:
- To investigate the role of zinc ions (Zn(II)) as probes for amyloid structure in Abeta peptide segments (Abeta(13-21)).
- To determine how Zn2+ coordination environments affect the rate of self-assembly and amyloid morphology.
- To elucidate the specific binding interactions of Zn2+ with histidine residues (His13/His14) during amyloid formation.
Main Methods:
- X-ray absorption spectroscopy (XAS) to characterize Zn2+ coordination environments.
- Studying the self-assembly kinetics of Abeta(13-21) in the presence of Zn2+.
- Analyzing the resulting amyloid morphologies using microscopy techniques (implied).
Main Results:
- Zn2+ specifically controls the self-assembly rate of Abeta(13-21).
- Distinct Zn2+ coordination environments dramatically regulate amyloid morphology.
- A single histidine residue (His13) is sufficient for productive Zn2+ coordination in typical fiber formation.
- The His13/His14 dyad allows access to a different Zn2+ coordination environment, stabilizing sheet/sheet associations and promoting ribbon/tube formation.
Conclusions:
- Zinc ions serve as effective probes for understanding amyloid structure and assembly.
- The coordination environment of Zn2+ plays a critical role in dictating amyloid morphology.
- Specific histidine residues in Abeta peptides mediate Zn2+-dependent structural transitions during amyloidogenesis.
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