Methionine Oxidation and Prion Protein Stability
Author Information
Author(s): Colombo Giorgio, Meli Massimiliano, Morra Giulia, Gabizon Ruth, Gasset María
Primary Institution: Isto di Chimica del Riconoscimento Molecolare, Consiglio Nazionale delle Ricerche, Milano, Italy
Hypothesis
Does methionine oxidation play a role in the misfolding process of prion proteins?
Conclusion
The sulfoxidation of Helix-3 methionines destabilizes the prion protein's α-fold, potentially triggering its conversion to a pathogenic form.
Supporting Evidence
- The oxidation of methionine residues alters the dynamics and stability of the prion protein.
- Oxidation increases the flexibility of the protein, favoring alternative states.
- Sulfoxidation of methionines is a covalent signature for the infectious form of prion proteins.
- Changes in protein dynamics may facilitate the conversion to a pathogenic form.
Takeaway
When certain parts of a protein called methionines get oxidized, it makes the protein less stable and more likely to change into a harmful form.
Methodology
Molecular dynamics simulations were used to study the effects of methionine oxidation on the stability and dynamics of the prion protein.
Limitations
The study's results are qualitative due to limitations in the time-scales simulated at room temperature.
Digital Object Identifier (DOI)
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