Structural plasticity of helical nanotubes based on coiled-coil assemblies

Area of Science:

• Biochemistry
• Structural Biology
• Materials Science

Background:

• Protein quaternary structures can evolve significantly with conserved sequences.
• The evolutionary pathways for such structural divergence remain largely unknown.
• Understanding these pathways is crucial for de novo design of peptide assemblies.

Purpose of the Study:

• To investigate how minor sequence modifications impact self-assembled peptide structures.
• To provide a model system for understanding evolutionary supramolecular structural changes.
• To explore the potential for de novo design of synthetic peptide assemblies.

Main Methods:

• Design of two synthetic 29-residue alpha-helical peptides.
• Spontaneous self-assembly into helical nanotubes in vitro.
• Near-atomic resolution analysis using electron cryomicroscopy with direct electron detection.

Main Results:

• Conservative changes in one or two amino acids induced significant quaternary structure alterations.
• Peptide assemblies demonstrated switchable behavior between two distinct forms.
• Near-atomic resolution revealed detailed structural changes.

Conclusions:

• Minor sequence variations can lead to substantial changes in supramolecular structure.
• This system serves as a framework for studying evolutionary structural divergence.
• Findings have implications for the de novo design of functional synthetic peptide assemblies.