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PMID: 15045026 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Dissection and design of yeast prions.

PLoS biology ·Vol. 2 ·No. 4 ·2004-04-00 ·Pages E86

Osherovich LZ, Cox BS, Tuite MF, Weissman JS

Abstract

Many proteins can misfold into beta-sheet-rich, self-seeding polymers (amyloids). Prions are exceptional among such aggregates in that they are also infectious. In fungi, prions are not pathogenic but rather act as epigenetic regulators of cell physiology, providing a powerful model for studying the mechanism of prion replication. We used prion-forming domains from two budding yeast proteins (Sup35p and New1p) to examine the requirements for prion formation and inheritance. In both proteins, a glutamine/asparagine-rich (Q/N-rich) tract mediates sequence-specific aggregation, while an adjacent motif, the oligopeptide repeat, is required for the replication and stable inheritance of these aggregates. Our findings help to explain why although Q/N-rich proteins are relatively common, few form heritable aggregates: prion inheritance requires both an aggregation sequence responsible for self-seeded growth and an element that permits chaperone-dependent replication of the aggregate. Using this knowledge, we have designed novel artificial prions by fusing the replication element of Sup35p to aggregation-prone sequences from other proteins, including pathogenically expanded polyglutamine.

MeSH Terms
Amino Acid Motifs DNA Replication Epigenesis, Genetic Fungal Proteins/chemistry Genes, Fungal Molecular Chaperones/chemistry Molecular Sequence Data Mutation Oligopeptides/chemistry Peptide Termination Factors Peptides/chemistry Plasmids/metabolism Polymers/chemistry Prions/chemistry Protein Folding Protein Structure, Tertiary Saccharomyces cerevisiae/metabolism Saccharomyces cerevisiae Proteins/chemistry Sequence Analysis, DNA
Chemicals
Fungal Proteins Molecular Chaperones Oligopeptides Peptide Termination Factors Peptides Polymers Prions SUP35 protein, S cerevisiae Saccharomyces cerevisiae Proteins polyglutamine
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Osherovich Lev Z
Department of Cellular and Molecular Pharmacology and Howard Hughes Medical Institute, University of California, San Francisco, USA. lxoshe@itsa.ucsf.edu
Cox Brian S
Tuite Mick F
Weissman Jonathan S
Conflict of Interest

The authors have declared that no conflicts of interest exist.

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Article Info
Journal
PLoS biology
Abbr.
PLoS Biol
ISSN
1545-7885
DOI
10.1371/journal.pbio.0020086
Email
lxoshe@itsa.ucsf.edu
Published
2004-04-00
Epub
2004-00-23
Pages
E86
Language
English
Region
United States
NLM ID
101183755
PMCID
PMC374241
Subset
IM
Databases
RefSeq
NC_014170, NP_010319, NP_010457, NP_010496, NP_013074, NP_015098
Corrections
CommentIn
PMID: 15094820
External Links
PubMed source DOI: 10.1371/journal.pbio.0020086 PMC Full Text View journal details
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