pH-Driven Polymorphism of Insulin Amyloid-Like Fibrils

Area of Science:

• Biochemistry
• Structural Biology
• Protein Misfolding Diseases

Background:

• Prions are infectious proteins causing distinct diseases through conformational changes.
• Prion-like self-propagation is increasingly observed in amyloid structures.
• Understanding factors driving amyloid strain formation is crucial for disease research.

Purpose of the Study:

• To investigate the formation of different insulin amyloid strains.
• To explore the influence of pH on insulin fibril structure and propagation.
• To identify potential factors controlling amyloid strain diversity.

Main Methods:

• Cultured two types of insulin amyloid-like fibrils under slightly different pH conditions.
• Utilized infrared spectroscopy to characterize fibril structures.
• Assessed the self-propagation capabilities of the distinct fibril types.

Main Results:

• Two distinct insulin amyloid fibril types with unique infrared spectra were formed.
• Both fibril types demonstrated self-propagation of their conformational templates.
• The low-pH induced strain showed structural similarity to previously reported insulin amyloid strains.

Conclusions:

• Slight pH variations can induce distinct insulin amyloid strains.
• Insulin amyloid strains exhibit prion-like self-propagation.
• A shift in insulin monomer-dimer equilibrium is a potential mechanism for strain control.