"Prion-proof" for [PIN+]: infection with in vitro-made amyloid aggregates of Rnq1p-(132-405) induces [PIN+]

J Mol Biol. 2007 Jan 19;365(3):773-82. doi: 10.1016/j.jmb.2006.10.069. Epub 2006 Oct 25.


Prions are self-propagating, infectious protein conformations. The mammalian prion, PrP(Sc), responsible for neurodegenerative diseases like bovine spongiform encephalopathy (BSE; "mad cow" disease) and Creutzfeldt-Jakob's disease, appears to be a beta-sheet-rich amyloid conformation of PrP(c) that converts PrP(c) into PrP(Sc). However, an unequivocal demonstration of "protein-only" infection by PrP(Sc) is still lacking. So far, protein only infection has been proven for three prions, [PSI(+)], [URE3] and [Het-s], all of fungal origin. Considerable evidence supports the hypothesis that another protein, the yeast Rnq1p, can form a prion, [PIN(+)]. While Rnq1p does not lose any known function upon prionization, [PIN(+)] has interesting positive phenotypes: facilitating the appearance and destabilization of other prions as well as the aggregation of polyglutamine extensions of the Huntingtin protein. Here, we polymerize a Gln/Asn-rich recombinant fragment of Rnq1p into beta-sheet-rich amyloid-like aggregates. While the method used for [PSI(+)] and [URE3] infectivity assays did not yield protein-only infection for the Rnq1p aggregates, we did successfully obtain protein-only infection by modifying the protocol. This work proves that [PIN(+)] is a prion mediated by amyloid-like aggregates of Rnq1p, and supports the hypothesis that heterologous prions affect each other's appearance and propagation through interaction of their amyloid-like regions.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Amyloid / metabolism*
  • Kinetics
  • Prions / chemistry*
  • Prions / metabolism*
  • Protein Structure, Quaternary
  • Recombinant Proteins / metabolism
  • Saccharomyces cerevisiae / cytology
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / chemistry*
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Temperature
  • Transformation, Genetic


  • Amyloid
  • Prions
  • RNQ1 protein, S cerevisiae
  • Recombinant Proteins
  • Saccharomyces cerevisiae Proteins