Microsecond sub-domain motions and the folding and misfolding of the mouse prion protein

Elife. 2019 Apr 26:8:e44766. doi: 10.7554/eLife.44766.


Protein aggregation appears to originate from partially unfolded conformations that are sampled through stochastic fluctuations of the native protein. It has been a challenge to characterize these fluctuations, under native like conditions. Here, the conformational dynamics of the full-length (23-231) mouse prion protein were studied under native conditions, using photoinduced electron transfer coupled to fluorescence correlation spectroscopy (PET-FCS). The slowest fluctuations could be associated with the folding of the unfolded state to an intermediate state, by the use of microsecond mixing experiments. The two faster fluctuations observed by PET-FCS, could be attributed to fluctuations within the native state ensemble. The addition of salt, which is known to initiate the aggregation of the protein, resulted in an enhancement in the time scale of fluctuations in the core of the protein. The results indicate the importance of native state dynamics in initiating the aggregation of proteins.

Keywords: Native state dynamics; PET-FCS; dry molten globule; microsecond fluctuations; microsecond mixing; molecular biophysics; mouse prion protein; none; structural biology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Kinetics
  • Mice
  • Prion Proteins / chemistry*
  • Prion Proteins / metabolism*
  • Protein Conformation
  • Protein Folding*
  • Spectrum Analysis


  • Prion Proteins
  • Prnp protein, mouse

Grants and funding

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.