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Amyloid fibrillogenesis: themes and variations
1Department of Neurology, Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. rochet@cnd.bwh.harvard.edu
Current Opinion in Structural Biology
|February 19, 2000
Summary
Protein self-assembly into amyloid fibrils is better understood, revealing common pathways for both unfolded and globular proteins. Structural models illuminate fibril formation and prefibrillar intermediates.
Area of Science:
- Biochemistry
- Structural Biology
- Biophysics
Background:
- Amyloid fibrils are protein aggregates implicated in various diseases.
- Understanding protein self-assembly into fibrils is crucial for disease mechanism elucidation.
- Recent advances have shed light on the initial steps of fibril formation.
Purpose of the Study:
- To summarize recent progress in understanding protein fibril formation.
- To highlight commonalities and variations in amyloid self-assembly pathways.
- To discuss the role of partially structured conformations in fibrillization.
Main Methods:
- Characterization of oligomeric prefibrillar intermediates (morphology, temporal evolution).
- Development of three-dimensional models using biophysical techniques.
- Computational methods for structural analysis.
Main Results:
- Both natively unfolded and globular proteins can initiate fibrillization.
- Partially structured conformations are key intermediates.
- Common features identified across different amyloid self-assembly pathways.
- Subtle variations explain differences between distinct amyloid fibrils.
Conclusions:
- Significant progress has been made in understanding protein fibril formation.
- A unified view of amyloid self-assembly pathways is emerging.
- Structural insights into fibril formation are advancing rapidly.