NIGMS grantee Susan Lindquist, Ph.D., and her colleagues at the University of Chicago have recently demonstrated a process in yeast that may help researchers finally pin down the infectious agent that causes a group of devastating neurological diseases called transmissible spongiform encephalopathies (TSEs). Over the years, scientific evidence has accumulated that misfolded protein particles, called prions (for proteinaceous infectious particles), are responsible for transmitting these diseases, which include the so-called "mad cow disease" that has recently shaken Europe.
So far, however, the role of prions is still the subject of scientific debate because no researcher has yet been able to synthesize prions that are infectious. Enter Dr. Lindquist, who has been funded by NIGMS for many years to study molecules called "hsps" (for heat-shock proteins) that assist, or "chaperone," protein folding.
In a series of experiments that will speed understanding of the self-propagating protein misfolding characteristic of TSEs, Dr. Lindquist and her colleagues have shown that, in yeast, the mere presence of a prion-like protein particle (Sup35) can cause newly synthesized Sup35 proteins to aggregate, presumably by misfolding. This occurs without any alteration of the DNA. The changes in the Sup35 protein structure are dependent on the concentration of a heat-shock protein, called Hsp 104. The discovery of this rather surprising new function for Hsp 104 should be very important in helping researchers sort out the mechanism by which the misfolding is passed on.
In addition to showing that these prionlike protein particles can pass on a trait by simply "being there," Dr. Lindquist and her colleagues believe this work holds broad implications for the field of genetics. The particles, like mammalian prions, behave like a completely new mode of inheritance that may quite possibly operate in a wide variety of organisms. The researchers speculate that other genetic phenomena that have been poorly understood up to now may depend on similar types of self-propagating alternative protein structures.
Patino MM, Liu J-J, Glover JR, Lindquist S. Support for the Prion Hypothesis for Inheritance of a Phenotypic Trait in Yeast. Science 1996;273:622-6.
Reporters may call the NIGMS Office of Communications and Public Liaison at (301) 496-7301 to obtain the name of a scientist in the NIGMS Division of Genetics and Developmental Biology who can comment on this work.
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8/9/2018 5:30 PM
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