Amyloid aggregates of the HET-s prion protein are infectious
AUTOR(ES)
Maddelein, Marie-Lise
FONTE
The National Academy of Sciences
RESUMO
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.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=124243Documentos Relacionados
- Domain organization and structure–function relationship of the HET-s prion protein of Podospora anserina
- The protein product of the het-s heterokaryon incompatibility gene of the fungus Podospora anserina behaves as a prion analog
- Sexual transmission of the [Het-s] prion leads to meiotic drive in Podospora anserina
- Alzheimer disease and the prion disorders amyloid beta-protein and prion protein amyloidoses.
- The environmental dependency of protein folding best explains prion and amyloid diseases