Related Experiment Video
Updated: Jun 12, 2025
08:53
Characterization of pH-Dependent Reversible Self-Assembly of Amyloid Beta 1-40-Coated Gold Colloids
Published on: March 21, 2025
586
Intrinsic conformational preference in the monomeric protein governs amyloid polymorphism
Anjali Giri1, Mily Bhattacharya1
1Department of Chemistry and Biochemistry, Thapar Institute of Engineering and Technology, Patiala-147004, Punjab, India. mily.bhattacharya@thapar.edu.
Physical Chemistry Chemical Physics : PCCP
|September 24, 2024
Summary
Protein monomer structure before aggregation dictates the final fibril shape, leading to amyloid polymorphism. Understanding these initial conformational preferences is key to explaining diverse amyloid structures.
Area of Science:
- Biochemistry and Molecular Biology
- Structural Biology
- Biophysics
Background:
- Protein self-assembly leads to diverse aggregate structures.
- Amyloid polymorphs arise from heterogeneous protofibril packing.
- The role of initial monomer conformation in polymorphism is unclear.
Purpose of the Study:
- Investigate how initial monomer conformation influences fibrillar polymorphism.
- Determine if monomeric conformational preferences dictate aggregation pathways.
- Establish the link between early monomer states and amyloid strain diversity.
Main Methods:
- Utilized fluorescence, FT-IR, and Raman spectroscopy.
- Employed dynamic light scattering and electron microscopy.
- Analyzed aggregation-competent ovalbumin monomers.
Main Results:
- Intrinsic monomer conformation dictates fibrillar polymorphism.
- Conformationally diverse monomers, formed via electrostatic and hydrophobic interactions, promote polymorphism.
- Monomer conformational fingerprints persist throughout aggregation.
Conclusions:
- Initial monomer conformation is a critical determinant of amyloid polymorphism.
- Understanding early conformational states provides insight into amyloid strain diversity.
- This finding has implications for diseases associated with protein aggregation.
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