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Interactions with and Membrane Permeabilization of Brain Mitochondria by Amyloid Fibrils
Published on: September 28, 2019
Raman optical activity study on insulin amyloid- and prefibril intermediate.
Shigeki Yamamoto1, Hitoshi Watarai
1Institute of Organic Chemistry and Biochemistry, Academy of Sciences, Prague, Czech Republic.
Chirality
|December 20, 2011
Summary
Bovine insulin amyloid fibrils were studied using Raman optical activity (ROA). ROA revealed that native alpha-helices convert to beta-sheets during amyloid formation, with intermediates showing distinct structural features.
Area of Science:
- Biophysics
- Protein Chemistry
- Spectroscopy
Background:
- Amyloid fibrils are associated with various diseases.
- Understanding protein misfolding and aggregation is crucial for disease research.
- Bovine insulin serves as a model system for studying protein aggregation.
Purpose of the Study:
- To investigate the structural changes during bovine insulin amyloid fibril formation.
- To characterize the intermediate states during the renaturation process.
- To elucidate the conversion pathway from native insulin to amyloid fibrils.
Main Methods:
- Raman Optical Activity (ROA) spectroscopy was employed.
- ROA was used to analyze the secondary structure of native insulin, amyloid fibrils, and renaturing intermediates.
- Spectral analysis focused on characteristic peaks associated with alpha-helix, beta-sheet, and turn structures.
Main Results:
- Amyloid fibrils exhibited ROA signals characteristic of beta-sheet structures and turn motifs.
- The hydrated alpha-helix signal of native insulin was absent in amyloid fibrils, indicating structural conversion.
- Intermediate states displayed unique ROA features distinct from both native and amyloid states, lacking poly(L-proline) II helix signals.
Conclusions:
- Amyloid formation involves the conversion of native hydrated alpha-helices to parallel beta-sheet structures with turns.
- Intermediate states represent a partially unfolded structure preceding beta-sheet formation.
- ROA is a powerful tool for monitoring protein structural transitions during amyloidogenesis and renaturation.
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