Afanasieva EG, et al. (2011) Molecular Basis for Transmission Barrier and Interference between Closely Related Prion Proteins in Yeast. J Biol Chem 286(18):15773-80
Abstract: Replicating amyloids, called prions, are responsible for transmissible neurodegenerative diseases in mammals and some heritable phenotypes in fungi. The transmission of prions between species is usually inhibited, being highly sensitive to small differences in amino acid sequence of the prion-forming proteins. To understand the molecular basis of this prion interspecies barrier, we studied the transmission of the [PSI+] prion state from Sup35 of Saccharomyces cerevisiae to hybrid Sup35 proteins with prion-forming domains from four other closely related Saccharomyces species. While all the hybrid Sup35 proteins could adopt a prion form in S. cerevisiae, they could not readily acquire the prion form from the [PSI+] prion of S. cerevisiae. Expression of the hybrid Sup35 proteins in S. cerevisiae [PSI+] cells often resulted in loss of the native [PSI+] prion. Furthermore, all hybrid Sup35 proteins showed different patterns of interaction with the native [PSI+] prion in terms of co-polymerization, acquisition of the prion state and induced prion loss, all of which were also dependent on the [PSI+] variant. The observed loss of S. cerevisiae [PSI+] can be related to inhibition of prion polymerization of S. cerevisiae Sup35 and formation of a non-heritable form of amyloid. We have therefore identified two distinct molecular origins of prion transmission barriers between closely sequence-related prion proteins: first the inability of heterologous proteins to co-aggregate with host prion polymers, and second acquisition by these proteins of a non-heritable amyloid fold.
| Status: Published | Type: Journal Article | PubMed ID: 21454674 |
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| Topics | Genes linked to topics |
|---|---|
| SUP35 | |
| Cross-species Expression | |
| Disease Gene Related | |
| Function/Process | |
| Fungal Related Genes/Proteins | |
| Mutants/Phenotypes | |
| Other Features | |
| Primary Literature | |
| Protein Sequence Features | |
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