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  • Review Article
  • Published:

Propagation of yeast prions

Nature Reviews Molecular Cell Biology volume 4, pages 878–890 (2003)Cite this article

Key Points

  • Prions are alternative conformers of certain proteins that have the property of promoting the folding or re-folding of the normal form into the prion conformer.

  • This property renders them self-replicating, defined as an increase in numbers by self-copying.

  • In yeast, this property makes prion forms of proteins heritable. Very often, the presence of the prion is associated with a new phenotype, so the protein becomes a genetic determinant. In mammals, the same properties of self-replication and a new phenotype or associated symptoms make it a protein-only agent of infectious disease.

  • The sequences of amino acids in peptides that allow prion conformers to occur have been studied in three yeast proteins. Removal of the so-called prion-forming domain (PrD) removes the ability to form and propagate prions.

  • Like mammalian prions, yeast prions within a single protein family come in more than one self-perpetuating variety, implying that there are different prion conformers possible in any one protein and that each conformer is able to replicate its own structure when converting normal molecules to a prion form.

  • As occurs in mammals, there is a species barrier to prion transmission in yeast. Homologous proteins from different species form their own unique prion conformers, but are mostly unable to convert the homologous protein of a different species to its prion form. The species barrier subsists in a definable region of the prion-forming domains.

  • Yeast prions all depend on the chaperone protein Hsp104 for their propagation, but not for their de novo conversion or incorporation into pre-existing prion aggregates. Other proteins, some of them Hsp70 or Hsp40 chaperones, also affect the stability or creation of prions.

  • All yeast prion-forming proteins so far described contain regions that are rich in glutamine (Q) or asparagine (N) residues, or both. They have this in common with many amyloid-forming proteins that are responsible for, or associated with, a variety of human diseases.

Abstract

Prion proteins have been implicated in various human neurodegenerative disorders and form amyloid deposits in the diseased brain. Uniquely, prion proteins seem to be able to propagate this altered conformational state, generating more of the prion form of the protein and acting as infectious agents. The discovery in yeast of prion proteins that can be inherited stably through generations of cell division provides us with an experimental model that is allowing the mysteries of how prions are propagated to be unravelled.

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Figure 1: The yeast prion-forming domain of Sup35.
Figure 2: The yeast prion-forming domain of Ure2.
Figure 3: Overview of yeast prion propagation: concept of propagons, their existence, replication and cell-to-cell transmission.
Figure 4: Model for yeast prion conversion and propagation?

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Acknowledgements

The authors' work on yeast prions has received long-term support from the Wellcome Trust and the Biotechnology and Biological Sciences Research Council. We would like to thank members of the Tuite laboratory for their comments on the manuscript.

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Authors and Affiliations

  1. Department of Biosciences, University of Kent, Canterbury, CT2 7NJ, Kent, UK

    Mick F. Tuite & Brian S. Cox

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  1. Mick F. Tuite
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Correspondence to Mick F. Tuite.

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DATABASES

SwissProt

Het-s

PrP

Saccharomyces Genome Database

Hsp104

Rnq1

Sla1

SSA1

Ssb1

Ssb2

SUP4

SUP16

SUP35

URE2

FURTHER INFORMATION

Mick Tuite's laboratory

Glossary

EPIGENETIC

Any heritable influence (in the progeny of cells or of individuals) on chromosome or gene function that is not accompanied by a change in DNA sequence.

OCHRE SUPPRESSOR

Mutations usually in a transfer RNA gene that allow insertion of one of several alternative amino acids into a polypeptide chain at the site of a premature ochre (UAA) chain-termination codon.

AMYLOID FIBRES

Insoluble, relatively inert fibres that are resistant to proteolysis, made from proteins in a β-pleated structure.

BIOLISTIC TRANSFORMATION

A method for introducing DNA (or in this case prion proteins) into the cell by bombardment with DNA- (or protein)-coated gold or tungsten particles.

DOMINANT-NEGATIVE

A dominant mutant allele of a gene that confers the phenotype of a null mutation in that gene.

HOMOPOLYMER TRACT

A region of any polymer that is made up of only one type of constitutional repeating unit. Cellulose, for example, contains only glucose as the monomeric unit.

SONICATION

The process by which samples are exposed to ultrasonic pressure waves (∼20 kHz) to disperse material into smaller aggregates or assemblies.

CHAPERONE

A protein that facilitates protein folding or promotes assembly of multisubunit complexes. Chaperones can also prevent aggregation of unassembled protein subunits or of partially folded protein domains or they can disaggregate previously formed aggregates.

AAA+ SUPERFAMILY

A family of proteins that share a homologous ATPase module. Proteins from this family participate in diverse cellular processes, including membrane traffic, proteolysis, DNA replication and chaperone functions.

NANOTECHNOLOGY

Any technological development that exceeds standard lower size limits of modern microfabrication techniques (hundreds of nanometres or less).

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Tuite, M., Cox, B. Propagation of yeast prions. Nat Rev Mol Cell Biol 4, 878–890 (2003). https://doi.org/10.1038/nrm1247

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