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Prion profits

Prions may not just be culprits in disease -- they may also do some good, new research shows. Proteins prone to morph into prions are widespread in yeast, and may benefit the organism by helping it adapt to a changing environment, scientists report in this week's Cell. Prion histology Image: Wikimedia CommonsThe results are "fascinating," and "biologically very significant," said Liming Li, a biochemist at Northwestern University who studies yeast prions but was not involved in the research. T

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Prions may not just be culprits in disease -- they may also do some good, new research shows. Proteins prone to morph into prions are widespread in yeast, and may benefit the organism by helping it adapt to a changing environment, scientists report in this week's Cell.
Prion histology
Image: Wikimedia Commons
The results are "fascinating," and "biologically very significant," said Liming Li, a biochemist at Northwestern University who studies yeast prions but was not involved in the research. The findings bolster the idea that some prions play a role in epigenetic regulation of gene expression, she said. Previous studies showed that three or four yeast proteins could form prions, but Susan Lindquist, a molecular biologist at the Whitehead Institute in Cambridge, Mass., and her colleagues wanted to see whether prion-forming proteins were widespread in yeast. The team surveyed the genome for traits common to known prions-- regions rich in glutamine and asparagine, and overall fewer highly charged amino acids. The screening revealed more than 200 proteins that fulfilled the criteria. Next, they wanted to see how many of these prion candidates actually transformed into prions in vivo and in vitro. Since most tests to determine whether a protein is a prion give only part of the picture, the group conducted a battery of tests on 94 of the likeliest candidates, said Whitehead molecular biologist Simon Alberti, a coauthor on the study. First, they investigated whether the proteins formed a ribbon-like structure in yeast cells-- a characteristic of prions, said Randal Halfmann, also a Whitehead molecular biologist and coauthor. Next, they tested whether candidate proteins could switch between two different versions-- a functional and a non-functional form, in which the proteins clump together to form aggregates. "In order to be a prion, a protein needs to be able to switch between two states," he said. Using these criteria, the researchers concluded that 19 of the 94 candidates formed prions. Since prions appeared to be much more prevalent in yeast than they had expected, the group speculated that the enigmatic proteins may play a useful biological role. They investigated one protein, Mot3, which helps build the cell wall in yeast. In its normal, functional form, Mot3 makes a softer cell wall, while the prion version builds a stiffer wall. In good growing conditions, "most of the yeast [cells] don't want to have a very strong cell wall, because they're growing fast," and thick cell walls inhibit cell growth and division, Halfmann said. However, when the going gets rough, having a few members of the colony with a stiff cell wall may increase the chances of survival. Proteins that can switch from one form to the other allow the cells in a yeast colony to "hedge their bets," increasing their heterogeneity in order to be adaptable to a wider range of environmental conditions, he said. The researchers suspect the results may have implications beyond yeast. "It's certainly possible that things like this can happen to more complex organisms. We've started a few assays to look for prions in other organisms," Halfmann said.
**__Related stories:__***linkurl: Prompting prions;https://www.the-scientist.com/blog/display/54929/
[1st April 2009]*linkurl:Prion protein aids bone marrow;https://www.the-scientist.com/news/display/23021/
[31st January 2006]*linkurl:Prion hypothesis proven?;https://www.the-scientist.com/article/display/22653/
[21st April 2005]
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