Distinct β-sheet structure in protein aggregates determined by ATR-FTIR spectroscopy.

Area of Science:

• Biochemistry
• Spectroscopy
• Structural Biology

Background:

• Protein aggregation is implicated in various diseases.
• Understanding the structural changes during protein aggregation is crucial.
• Various forms of protein aggregates exist, including amyloid fibrils and inclusion bodies.

Purpose of the Study:

• To investigate the secondary structure of diverse protein aggregates using ATR-FTIR.
• To identify common structural features across different types of protein aggregates.
• To elucidate the structural basis of protein aggregation.

Main Methods:

• Attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) was employed.
• Multiple protein aggregate types were analyzed: amyloid fibrils, inclusion bodies, folding aggregates, soluble oligomers, and stressed cell extracts.
• Spectral analysis focused on identifying characteristic band positions related to secondary structure.

Main Results:

• All examined protein aggregates exhibited a distinct new beta structure characterized by lower-frequency band positions.
• This new beta structure arises from intermolecular interactions during the aggregation process.
• Native-like secondary structures and nonperiodic structures were also present alongside the new beta structure.
• Different aggregate types from the same protein displayed similar spectral features, suggesting a common precursor species.

Conclusions:

• Protein aggregation consistently induces a novel intermolecular beta-sheet structure.
• This structure is stabilized by stronger hydrogen bonds within the aggregates.
• The findings provide insights into the structural transformations occurring during protein aggregation.
• ATR-FTIR is a valuable tool for characterizing protein aggregate conformations.