What makes a protein sequence a prion?

PLoS Comput Biol. 2015 Jan 8;11(1):e1004013. doi: 10.1371/journal.pcbi.1004013. eCollection 2015 Jan.


Typical amyloid diseases such as Alzheimer's and Parkinson's were thought to exclusively result from de novo aggregation, but recently it was shown that amyloids formed in one cell can cross-seed aggregation in other cells, following a prion-like mechanism. Despite the large experimental effort devoted to understanding the phenomenon of prion transmissibility, it is still poorly understood how this property is encoded in the primary sequence. In many cases, prion structural conversion is driven by the presence of relatively large glutamine/asparagine (Q/N) enriched segments. Several studies suggest that it is the amino acid composition of these regions rather than their specific sequence that accounts for their priogenicity. However, our analysis indicates that it is instead the presence and potency of specific short amyloid-prone sequences that occur within intrinsically disordered Q/N-rich regions that determine their prion behaviour, modulated by the structural and compositional context. This provides a basis for the accurate identification and evaluation of prion candidate sequences in proteomes in the context of a unified framework for amyloid formation and prion propagation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence / physiology*
  • Amyloid / chemistry*
  • Amyloid / metabolism
  • Fungal Proteins / chemistry
  • Fungal Proteins / metabolism
  • Hydrophobic and Hydrophilic Interactions
  • Molecular Sequence Data
  • Prions / chemistry*
  • Prions / metabolism


  • Amyloid
  • Fungal Proteins
  • Prions

Grant support

This work was supported in part by grants BFU2010-14901 from Ministerio de Ciencia e Innovacion (Spain), by grant 2014-SGR 938 from AGAUR (Agencia de Gestio d'Ajuts Universitaris i de Recerca-Generalitat de Catalunya). The Switch Laboratory was supported by grants from VIB, University of Leuven, the Funds for Scientific Research Flanders (FWO), the Flanders Institute for Science and Technology (IWT) and the Federal Office for Scientific Affairs of Belgium (Belspo), IUAP P7/16. RS is the beneficiary of a contract from the Ramón y Cajal Programme (RYC-2011-07987) from Ministerio de Ciencia e Innovación. SV has been granted an ICREA-ACADEMIA award (Institució Catalana de Recerca I Estudis Avançats).