A designed beta-hairpin forming peptide undergoes a consecutive stepwise process for self-assembly into nanofibrils

Area of Science:

• Biochemistry
• Materials Science
• Biophysics

Background:

• Peptide fibrogenesis is crucial for understanding amyloid diseases and designing self-assembling nanomaterials.
• Beta-hairpin forming peptides offer a model system for studying hierarchical self-assembly.

Purpose of the Study:

• To investigate the kinetics and mechanism of de novo designed T1 peptide fibrogenesis.
• To elucidate the cooperative steps involved in peptide aggregation and structural conversion.

Main Methods:

• Utilized light scattering (LS), circular dichroism (CD), fluorescence spectroscopy, and atomic force microscopy (AFM).
• Employed a de novo designed T1 peptide as a model system.

Main Results:

• Demonstrated a consecutive stepwise process in T1 peptide fibrogenesis with high cooperation.
• Observed sigmoidal time-courses for peptide aggregation, backbone conformational conversion, and sidechain rearrangement.
• Identified a dimensional size threshold for aggregates as a potential trigger for conformational conversion and beta-structural nucleus formation.

Conclusions:

• Peptide sidechain interactions facilitate regular alignment and suprastructure formation, in addition to triggering aggregation.
• The findings provide insights into the hierarchical self-assembly of beta-hairpin peptides.
• This research aids in designing beta-structural peptides for self-assembly into nanowires for nano-material applications.