In complimentary papers coming out in Science and Molecular Cell, researchers at the University of Chicago describe how prions--proteins that can exist in two different conformations and can pass their particular conformation from one generation to the next without any change in DNA--are modular. This discovery may convert these esoteric proteins into one of the most valuable tools in modern molecular biology.
A prion is a normal protein that has folded into an unusual shape. In its "prion state" the protein can entice other, healthy proteins of the same kind to adopt the misfolded prion form, a kind of protein misfolding chain reaction. Additionally, prions are both "infectious" and heritable--they are passed from generation to generation with no change in the nucleic acid sequence of the protein.
The researchers, led by Susan Lindquist, Ph.D., the Albert D. Lasker professor of molecular genetics & cell biology and Howard Hughes Investigator, found that the prion-determining region of prion proteinsthe part of the prion protein that misfoldscan be transplanted onto other proteins, causing them to become prion-like.
"We've discovered a method to create novel prions which ultimately can have a lot of applications," said Lindquist.
Previous research has shown that prions are composed of two subunits--the prion-determining region and a functional domain which performs some function. "Once the prion part misfolds it entices other proteins of the same kind to fold incorrectly and they can clump together," Lindquist said. "The functional part may still be active. But if its job needs to be done in a particular place, it can't get there because its stuck."
In her January 28 Science paper, Lindquist and postdoctoral fellow Liming Li created a novel prion by taking the prion-determining part of Sup35, a known yeast prion, and linking it to a mammalian hormone response factor.