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Characterization of pH-Dependent Reversible Self-Assembly of Amyloid Beta 1-40-Coated Gold Colloids
Published on: March 21, 2025
Conformational switching within individual amyloid fibrils
Natallia Makarava1, Valeriy G Ostapchenko, Regina Savtchenko
1Medical Biotechnology Center, University of Maryland Biotechnology Institute, Baltimore, MD 21201, USA.
The Journal of Biological Chemistry
|March 31, 2009
Summary
Amyloid fibrils can change their structure within a single fibril, even when encountering incompatible protein sequences. This conformational switching demonstrates amyloid
Area of Science:
- Biochemistry
- Structural Biology
- Molecular Biology
Background:
- Amyloid fibrils possess a highly ordered cross-beta-sheet core, crucial for their structure.
- It is generally assumed that individual amyloid fibrils maintain conformational uniformity.
Purpose of the Study:
- To investigate the conformational adaptability of amyloid structures within individual fibrils.
- To explore the mechanism of amyloid strain conversion when encountering incompatible substrates.
Main Methods:
- Utilized mammalian recombinant prion protein (PrP) in fibrillation reactions.
- Employed fibrillar templates with strain-specific conformations.
- Analyzed conformational changes in PrP variants during fibril elongation.
Main Results:
- Demonstrated that individual amyloid fibrils can undergo significant conformational switching.
- Observed conformational adaptation even with sequence mismatches between substrate and template.
- Showcased recruitment of heterologous PrP variants leading to altered amyloid strains within fibrils.
Conclusions:
- Amyloid structures exhibit remarkable adaptation potential, challenging the notion of uniform fibrils.
- Conformational switching within fibrils offers a mechanism for amyloid strain adaptation to new substrates.
- This study provides new insights into amyloid strain conversion, evolution, and the decoupling of catalytic activity from templating.
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