Zinc-binding structure of a catalytic amyloid from solid-state NMR

Area of Science:

• Biochemistry
• Structural Biology
• Materials Science

Background:

• Amyloids are protein structures found in both functional biological roles and pathological conditions.
• Amyloids possess properties suggesting early evolutionary significance and potential as advanced material backbones.
• Metalloamyloids, where metals interact with amyloid structures, require high-resolution structural data to understand their function.

Purpose of the Study:

• To determine the high-resolution structure of a zinc-bound metalloamyloid.
• To investigate the catalytic activity of this metalloamyloid in ester hydrolysis.
• To elucidate the molecular basis of metal-amyloid interactions and their influence on structure and function.

Main Methods:

• Utilized solid-state Nuclear Magnetic Resonance (NMR) spectroscopy.
• Employed structural bioinformatics for data analysis and model building.
• Characterized the self-assembly of peptide into amphiphilic parallel β-sheets forming stacked bilayers.

Main Results:

• Determined the structure of a zinc-bound metalloamyloid catalyzing ester hydrolysis.
• Observed unusual Zn²⁺-binding geometries involving bis-coordinated histidine residues bridging adjacent peptide strands.
• Identified an infinite metal-ligand chain formation along the fibril axis with a water-accessible site for catalysis.

Conclusions:

• Introduced a new class of materials termed metal-peptide frameworks.
• Demonstrated that metal ions stabilize amyloid structures, influencing ligand geometry and catalytic activity.
• Highlighted the intricate relationship between metal ions, amyloid structure, and catalytic function.