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Redefining what it means to be a prion
Date:4/2/2009

neurological diseases, including scrapie in sheep and goats, and Creutzfeldt-Jakob disease in humans. A few prions have also been found in model organisms, such as yeast.

Believing the number of prions in yeast is higher than the four identified, researchers in Lindquist's lab devised a high-throughput method to scan the entire yeast genome, detect probable prion-coding sequences, and confirm that the resulting proteins are in fact prions. Lindquist says, "The approach required a lot of assay development and a great deal of work but the results were very exciting."

The scan located about 200 candidate prion-coding sequences in the yeast genome. The top 100 candidate proteins were tested for up to three hallmarks of prions: their tendency in cells to form clumps that remain intact when exposed to a detergent capable of unfolding most proteins; the ability of the proteins to clump in a Petri dish in the absence other cellular factors; and the ability of the proteins to replicate indefinitely in cells.

Applying their set of tests, the researchers found 24 prion candidates meeting all three criteria. Included in that number were all four of the known yeast prions.

"No one had taken such a broad approach to look for prions in any genome," says Simon Alberti, a Lindquist postdoctoral researcher and co-author of the paper. "And the results from work in yeast cells, and the in vitro work overlapped and supported each other very nicely."

Alberti and Halfmann hypothesize that prions in yeast prepare individual organisms for changes in the environment. Prions in cells are known to switch back and forth between a clumping, infectious stage and a non-infectious stage. When yeast is stressed, this switching occurs at a higher rate, which may give the yeast a better chance to adapt to challenging conditions.

For example, if a grape dusted with yeast falls from the vine and into a puddle, the waterlogged yeast's environment
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Contact: Nicole Giese
giese@wi.mit.edu
617-258-6851
Whitehead Institute for Biomedical Research
Source:Eurekalert

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