Strain conformation controls the specificity of cross-species prion transmission in the yeast model
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Updated: Mar 15, 2026
High-throughput Screening for Protein-based Inheritance in S. cerevisiae
Published on: August 8, 2017
Anastasia V Grizel1,2,3, Aleksandr A Rubel1,2,3, Yury O Chernoff1,2,4
1a Laboratory of Amyloid Biology, St. Petersburg State University , St. Petersburg , Russia.
Abstract:
Transmissible self-assembled fibrous cross-β polymer infectious proteins (prions) cause neurodegenerative diseases in mammals and control non-Mendelian heritable traits in yeast. Cross-species prion transmission is frequently impaired, due to sequence differences in prion-forming proteins. Recent studies of prion species barrier on the model of closely related yeast species show that colocalization of divergent proteins is not sufficient for the cross-species prion transmission, and that an identity of specific amino acid sequences and a type of prion conformational variant (strain) play a major role in the control of transmission specificity. In contrast, chemical compounds primarily influence transmission specificity via favoring certain strain conformations, while the species origin of the host cell has only a relatively minor input. Strain alterations may occur during cross-species prion conversion in some combinations. The model is discussed which suggests that different recipient proteins can acquire different spectra of prion strain conformations, which could be either compatible or incompatible with a particular donor strain.
Insights
Prion transmission between species is limited by protein sequence identity and prion strain type. Chemical compounds can alter prion strain conformations, influencing transmission specificity more than host cell origin.
Area of Science:
- Biochemistry
- Molecular Biology
- Neuroscience
Background:
- Prions, infectious proteins forming cross-β polymers, cause neurodegenerative diseases and heritable traits.
- Cross-species prion transmission is often blocked by differences in prion-forming protein sequences.
Purpose of the Study:
- To investigate the factors controlling prion transmission specificity across species barriers.
- To understand the roles of protein sequence, prion strain, and host cell in prion propagation.
Main Methods:
- Utilized a model system of closely related yeast species to study prion transmission barriers.
- Analyzed the impact of protein sequence identity, prion conformational variants (strains), and chemical compounds on transmission specificity.
Main Results:
- Protein sequence identity and specific prion strain types are critical for cross-species prion transmission.
- Chemical compounds influence transmission by favoring specific prion strain conformations, with host cell origin having a minor role.
- Strain alterations can occur during cross-species conversion, leading to different recipient protein conformation spectra.
Conclusions:
- Prion transmission specificity is primarily determined by molecular compatibility between donor and recipient prion proteins and their conformational states.
- The host cell environment plays a secondary role compared to the intrinsic properties of the prions themselves.
