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Updated: Jun 3, 2026
High-throughput Screening for Protein-based Inheritance in S. cerevisiae
Published on: August 8, 2017
Sequence specificity and fidelity of prion transmission in yeast
Kathryn L Bruce1, Yury O Chernoff
1School of Biology and Institute for Bioengineering and Bioscience, Georgia Institute of Technology, 310 Ferst Drive, Atlanta, GA 30332-0230, USA.
Abstract:
Amyloid formation is a widespread feature of various proteins. It is associated with both important diseases (including infectious mammalian prions) and biologically positive functions, and provides a basis for structural "templating" and protein-based epigenetic inheritance (for example, in the case of yeast prions). Amyloid templating is characterized by a high level of sequence specificity and conformational fidelity. Even slight variations in sequence may produce a strong barrier for prion transmission. Yeast models provide useful insight into a mechanism of amyloid specificity and fidelity. Accumulating evidence indicates that cross-species prion transmission is controlled by the identity of short sequences (specificity stretches) rather than by the overall level of sequence identity. Location of the specificity stretches determines the location and/or size of the cross-β amyloid region that controls patterns of prion variants. In some cases of cross-species prion transmission, fidelity of variant reproduction is impaired, leading to the formation of new structural variants. We propose that such a variant switch may occur due to choice of the alternatively located secondary specificity stretches, when interaction between the primary stretches is impaired due to sequence divergence.
Insights
Protein amyloid formation underlies diseases and biological functions. Specific short sequences, not overall identity, control prion transmission and variant formation, even across species.
Area of Science:
- Biochemistry
- Structural Biology
- Molecular Biology
Background:
- Amyloid formation is a fundamental process in proteins, implicated in diseases like prion disorders and beneficial functions such as yeast prions.
- Amyloid templating exhibits high sequence specificity and conformational fidelity, crucial for structural inheritance.
- Yeast prion models offer valuable insights into the mechanisms governing amyloid specificity and fidelity.
Purpose of the Study:
- To investigate the role of specific sequence elements in controlling amyloid templating and cross-species prion transmission.
- To elucidate the mechanism by which sequence variations influence prion fidelity and variant formation.
Main Methods:
- Analysis of protein sequences and structural data related to amyloid formation.
- Utilizing yeast prion models to study cross-species transmission barriers and fidelity.
- Investigating the impact of sequence divergence on amyloid structure and propagation.
Main Results:
- Cross-species prion transmission is primarily dictated by short "specificity stretches" within protein sequences, rather than overall sequence identity.
- The location of these specificity stretches influences the amyloid region and prion variant patterns.
- Impaired interaction at primary specificity stretches due to sequence divergence can lead to the formation of new prion variants via alternative secondary stretches.
Conclusions:
- Short sequence elements are critical determinants of amyloid templating specificity and cross-species prion transmission.
- Sequence divergence can disrupt prion fidelity, potentially leading to the emergence of novel prion variants.
- Understanding these specificity mechanisms is key to comprehending prion diseases and protein-based inheritance.
