NR AVYB
AU Patel,B.K.; Liebman,S.W.
TI "Prion-proof" for [PIN+]: infection with in vitro-made amyloid aggregates of Rnq1p-(132-405) induces [PIN+].
QU Journal of Molecular Biology 2007 Jan 19; 365(3): 773-82
PT journal article; research support, n.i.h., extramural
AB Prions are self-propagating, infectious protein conformations. The mammalian prion, PrPsc, 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 PrPc that converts PrPc into PrPsc. However, an unequivocal demonstration of "protein-only" infection by PrPsc 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.
MH Amino Acid Sequence; Amyloid/*metabolism; Kinetics; Prions/*chemistry/*metabolism; Protein Structure, Quaternary; Recombinant Proteins/metabolism; Saccharomyces cerevisiae/cytology/*metabolism; Saccharomyces cerevisiae Proteins/*chemistry/*metabolism; Temperature; Transformation, Genetic
AD Department of Biological Sciences, Laboratory of Molecular Biology, University of Illinois, Chicago, IL 60607, USA
SP englisch
PO England