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Updated: Jun 14, 2026
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Atomic Scale Structural Studies of Macromolecular Assemblies by Solid-state Nuclear Magnetic Resonance Spectroscopy
Published on: September 17, 2017
Prion fibrillization is mediated by a native structural element that comprises helices H2 and H3
Miquel Adrover1, Kris Pauwels, Stephanie Prigent
1MRC National Institute for Medical Research, The Ridgeway, London NW7 1AA, United Kingdom.
The Journal of Biological Chemistry
|April 9, 2010
Summary
The prion protein's (PrP) H2H3 region forms a stable unit that readily misfolds into amyloid fibers. This isolated region acts as a seed, initiating the aggregation process in prion protein misfolding.
Area of Science:
- Neurodegenerative diseases
- Protein misfolding
- Prion protein (PrP) structure and aggregation
Background:
- Prion protein (PrP) misfolding and aggregation cause fatal neurodegenerative diseases.
- While PrP structures are known, the mechanisms of misfolding remain unclear.
Purpose of the Study:
- To investigate the role of the H2H3 hairpin region in PrP misfolding and aggregation.
- To elucidate the initial steps in the formation of pathogenic PrP species.
Main Methods:
- Biochemical analysis of the isolated H2H3 region of PrP.
- Structural stability assays.
- Amyloid fibril formation studies.
- Comparative analysis with full-length PrP.
Main Results:
- The H2H3 region of PrP is a stable, independently folded unit retaining secondary and tertiary structure.
- Isolated H2H3 is highly fibrillogenic, forming amyloid fibers similar to full-length PrP.
- H2H3 fibrillization, unlike full-length PrP, is accompanied by aggregate formation.
Conclusions:
- The H2H3 region acts as an aggregation seed in PrP misfolding.
- A "banana-peeling" mechanism is proposed, where H2H3 exposure initiates conversion to beta-rich structures.
- Understanding this mechanism may offer new therapeutic targets for prion diseases.
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