Engineering β-sheet morphologies via metal cross-linking and side chain modifications.

Area of Science:

• Biochemistry
• Materials Science
• Structural Biology

Background:

• Natural and artificial β-sheet assemblies commonly exhibit helical structures due to peptide strand twisting.
• Structural disorder often prevents analysis of these assemblies using single crystal X-ray diffraction (SCD).

Purpose of the Study:

• To overcome challenges in analyzing helical peptide assemblies using SCD.
• To develop a method for creating ordered helical structures from β-sheet tapes.

Main Methods:

• Periodically cross-linking peptide strands within β-sheet tapes using metal coordination.
• Utilizing atomic force microscopy (AFM) and transmission electron microscopy (TEM) for structural observation.
• Employing single crystal X-ray diffraction (SCD) for detailed structural analysis.

Main Results:

• Successfully created perfectly ordered helical structures suitable for SCD analysis.
• Identified side chain interactions as the primary drivers of helical twisting.
• Demonstrated the ability to tune helical morphology, including the formation of double helices, by adjusting side chain substituents.

Conclusions:

• Metal-coordinated cross-linking enables precise structural control of β-sheet assemblies.
• Side chain engineering is a viable strategy for designing and tuning helical peptide structures.
• This approach significantly advances the field of peptide engineering and structural analysis.