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Updated: Aug 7, 2026
05:48
Rapid Generation of Amyloid from Native Proteins In vitro
Published on: December 5, 2013
Interpreting the aggregation kinetics of amyloid peptides
Riccardo Pellarin1, Amedeo Caflisch
1Department of Biochemistry, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.
Journal of Molecular Biology
|June 27, 2006
Summary
Protein stability influences amyloid fibril formation. Enhancing the stability of beta-sheet prone states shifts aggregation from disordered to fibrillar pathways, impacting disease mechanisms and functional amyloid assembly.
Area of Science:
- Structural Biology
- Biophysics
- Computational Biology
Background:
- Amyloid fibrils, insoluble beta-sheet protein aggregates, are linked to neurodegenerative diseases.
- The precise mechanisms of oligomer formation and protein stability's role in amyloid aggregation kinetics remain unclear.
Purpose of the Study:
- To investigate the kinetics and pathways of amyloid fibril formation using a coarse-grained polypeptide model.
- To explore how varying the stability of amyloid-competent states influences aggregation processes.
Main Methods:
- Utilized a coarse-grained model of an amphipathic polypeptide with defined beta-prone and beta-protected states.
- Performed simulations to analyze aggregation kinetics and fibril formation pathways under different stability conditions.
Main Results:
- Increased stability of the beta-prone state promoted fibrillogenesis over disordered aggregation.
- Oligomeric intermediates were observed during fibril formation, their presence depending on beta-prone state stability.
- The minimal fibril-forming aggregate originated from oligomer or monomer collisions, contingent on polypeptide stability.
Conclusions:
- Polypeptide stability is a critical determinant of amyloid aggregation pathways and kinetics.
- Simulation results offer molecular insights into diverse amyloid aggregation mechanisms and functional amyloid assembly rates.
Related Concept Videos
03:03Amyloid Fibrils
Amyloid fibrils are aggregates of misfolded proteins. Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils.
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
03:03Amyloid Fibrils
Amyloid fibrils are aggregates of misfolded proteins. Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils.
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...