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Identification of Two Early Folding Stage Prion Non-Local Contacts Suggested to Serve as Key Steps in Directing the Final Fold to Be Either Native or Pathogenic.
- Source :
-
International Journal of Molecular Sciences . Aug2021, Vol. 22 Issue 16, p8619-8619. 1p. - Publication Year :
- 2021
-
Abstract
- The initial steps of the folding pathway of the C-terminal domain of the murine prion protein mPrP(90–231) are predicted based on the sequential collapse model (SCM). A non-local dominant contact is found to form between the connecting region between helix 1 and β-sheet 1 and the C-terminal region of helix 3. This non-local contact nucleates the most populated molten globule-like intermediate along the folding pathway. A less stable early non-local contact between segments 120–124 and 179–183, located in the middle of helix 2, promotes the formation of a less populated molten globule-like intermediate. The formation of the dominant non-local contact constitutes an example of the postulated Nature's Shortcut to the prion protein collapse into the native structure. The possible role of the less populated molten globule-like intermediate is explored as the potential initiation point for the folding for three pathogenic mutants (T182A, I214V, and Q211P in mouse prion numbering) of the prion protein. [ABSTRACT FROM AUTHOR]
- Subjects :
- *PRION diseases
*PRIONS
*STRUCTURAL failures
*SUPPLY chain management
Subjects
Details
- Language :
- English
- ISSN :
- 16616596
- Volume :
- 22
- Issue :
- 16
- Database :
- Academic Search Index
- Journal :
- International Journal of Molecular Sciences
- Publication Type :
- Academic Journal
- Accession number :
- 152145319
- Full Text :
- https://doi.org/10.3390/ijms22168619