A micellar on-pathway intermediate step explains the kinetics of prion amyloid formation

PLoS Comput Biol. 2014 Aug 7;10(8):e1003735. doi: 10.1371/journal.pcbi.1003735. eCollection 2014 Aug.

Abstract

In a previous work by Alvarez-Martinez et al. (2011), the authors pointed out some fallacies in the mainstream interpretation of the prion amyloid formation. It appeared necessary to propose an original hypothesis able to reconcile the in vitro data with the predictions of a mathematical model describing the problem. Here, a model is developed accordingly with the hypothesis that an intermediate on-pathway leads to the conformation of the prion protein into an amyloid competent isoform thanks to a structure, called micelles, formed from hydrodynamic interaction. The authors also compare data to the prediction of their model and propose a new hypothesis for the formation of infectious prion amyloids.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid / chemistry
  • Amyloid / metabolism*
  • Kinetics
  • Micelles*
  • Models, Molecular*
  • Prions / chemistry*
  • Prions / metabolism*
  • Protein Conformation

Substances

  • Amyloid
  • Micelles
  • Prions

Grants and funding

This work has been supported by ANR grant MADCOW no. ANR-08-JCJC-0135-01 (France). EH has been partially supported by FONDECYT postdoctoral grant no. 3130318 (Chile). The authors thank INRIA for its financial support. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.