Osherovich, Lev Z. and Cox, Brian S. and Tuite, Mick F. and Weissman, Jonathan S. (2004) Dissection and design of yeast prions. PLoS Biology, 2 (4). pp. 442-451. ISSN 1544-9173. (doi:https://doi.org/10.1371/journal.pbio.0020086) (Full text available)
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.
|Additional information:||This article is freely available from PLoS Biology.|
|Divisions:||Faculties > Sciences > School of Biosciences > Protein Science Group|
|Depositing User:||Sue Davies|
|Date Deposited:||19 Dec 2007 17:52 UTC|
|Last Modified:||12 Jan 2017 19:10 UTC|
|Resource URI:||https://kar.kent.ac.uk/id/eprint/66 (The current URI for this page, for reference purposes)|