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March 29, 2004
Volume 82, Number 13
p. 8 |
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BIOCHEMISTRY
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A PRIORI PRIONS
Scientists use structural insights to synthesize artificial yeast prions |
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AALOK MEHTA |
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Researchers working with yeast have isolated two separate protein domains necessary for prion behavior—one responsible for growth, the other for inheritance—and used them to synthesize artificial yeast prions from scratch.
Biochemist Lev Z. Osherovich and colleagues at the University of California, San Francisco, and the University of Kent, in England, discovered the domains while conducting molecular biology studies on two naturally occurring yeast prions [PLoS Biol., published online March 23,
http://dx.doi.org/10.1371/journal.pbio.0020086].
Osherovich’s team found that a glutamine/asparagine-rich region allows yeast prions to aggregate and grow, but a separate conserved oligopeptide repeat sequence is needed for them to pass their traits on to future generations.
Osherovich postulates that the oligopeptide repeats provide binding sites for chaperone proteins, which are known to cleave aggregates into small, inheritable fragments. The findings help distinguish proteins that merely aggregate—forming clumps known as amyloids, which occur in Alzheimer’s and Huntington’s disease—from prions that are inherited.
To confirm their discoveries, the researchers successfully generated novel artificial prions by fusing the oligopeptide repeat sequence with aggregation-prone regions from other proteins.
“This research is one example—and it may well be general—showing the elements of what makes a prion a prion,” says Susan W. Liebman, a biology professor at the University of Illinois, Chicago.
Prion domains could be used to create hybrid proteins for medical studies, Osherovich suggests. By converting amyloid proteins into inheritable yeast prions, he says, “you get a powerful tool for screening for pharmaceutical activity."
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A PRION’S LIFE During growth, yeast prion monomers aggregate through interactions between glutamine/asparagine-rich sequences (blue). A separate oligopeptide repeat (orange) is required for division and inheritance. Researchers synthesized artificial prions by fusing the two sequences.
ADAPTED FROM PLoS BIOLOGY |
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Chemical & Engineering News
ISSN 0009-2347
Copyright © 2004 |
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