NR AHRR
AU Maddelein,M.L.; Dos Reis,S.; Duvezin-Caubet,S.; Coulary-Salin,B.; Saupe,S.J.
TI Amyloid aggregates of the HET-s prion protein are infectious
QU Proceedings of the National Academy of Sciences of the United States of America 2002 May 28; 99(11): 7402-7
KI Proc Natl Acad Sci U S A. 2002 Jul 9;99(14):9098-100. PMID: 12093925
PT journal article
AB The [Het-s] infectious element of the filamentous fungus Podospora anserina is a prion. We have recently reported that recombinant HET-s protein aggregates in vitro into amyloid fibers. In vivo, the protein aggregates specifically in the [Het-s] prion strains. Here, we show that biolistic introduction of aggregated recombinant HET-s protein into fungal cells induces emergence of the [Het-s] prion with a high frequency. Thus, we demonstrate that prion infectivity can be created de novo, in vitro from recombinant protein in this system. Although the amyloid filaments formed from HET-s could transmit [Het-s] efficiently, neither the soluble form of the protein nor amorphous aggregates would do so. In addition, we have found that (i) [Het-s] infectivity correlates with the ability to convert HET-s to amyloids in vitro, (ii) [Het-s] infectivity is resistant to proteinase K digestion, and (iii) HET-s aggregates formed in vivo in [Het-s] strains have the ability to convert the recombinant protein to aggregates. Together, our data designate the HET-s amyloids as the molecular basis of [Het-s] prion propagation.
MH Amyloid/chemistry/*metabolism; Biolistics; Endopeptidase K; Escherichia coli/genetics; Fungal Proteins/chemistry/isolation & purification/*metabolism; Prions/*metabolism/pathogenicity; Recombinant Proteins/chemistry/metabolism; Sordariales/growth & development/pathogenicity/*physiology; Support, Non-U.S. Gov't
AD Laboratoire de Genetique Moleculaire des Champignons, Institut de Biochimie et de Genetique Cellulaires, Unite Mixte de Recherche 5095, Centre National de la Recherche Scientifique, Universite de Bordeaux 2, France. ML.Maddelein@ibgc.u-bordeaux2.fr
SP englisch
PO USA