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

Fernando Bergasa‐caceres, Herschel A. Rabitz

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number8619
JournalInternational journal of molecular sciences
Volume22
Issue number16
DOIs
StatePublished - Aug 2 2021

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Keywords

  • Folding
  • Intermediate
  • Molten globule
  • Neuropathology
  • Pathway
  • Prion

Fingerprint

Dive into the research topics of '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'. Together they form a unique fingerprint.

Cite this