MCB Accepts, published online ahead of print on 2 November 2009

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Mol. Cell. Biol. doi:10.1128/MCB.01140-09
Copyright (c) 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Compositional determinants of prion formation in yeast

James A. Toombs, Blake R. McCarty, and Eric D. Ross^*

Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, Colorado 80523, USA

^* To whom correspondence should be addressed. Email: eric.ross{at}colostate.edu.

Numerous prions (infectious proteins) have been identified in yeast that result from conversion of soluble proteins into -sheet-rich amyloid-like protein aggregates. Yeast prion formation is driven primarily by amino acid composition. However, yeast prion domains are generally lacking in the bulky hydrophobic residues most strongly associated with amyloid formation, and are instead enriched in glutamines and asparagines. Glutamine/asparagine-rich domains are thought to be involved in both disease-related and beneficial amyloid formation. These domains are over-represented in eukaryotic genomes, but predictive methods have not yet been developed to efficiently distinguish between prion and non-prion glutamine/asparagine-rich domains. We have developed a novel in vivo assay to quantitatively assess how composition affects prion formation. Using our results, we have defined the compositional features that promote prion formation, allowing us to accurately distinguish between glutamine/asparagine-rich domains that can form prion-like aggregates and those that can not. Additionally, our results explain why traditional amyloid prediction algorithms fail to accurately predict amyloid formation by the glutamine/asparagine-rich yeast prion domains.