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UCSF scientists show prion shape affects nature of infection

UCSF scientists have demonstrated for the first time that a change in the folded shape of a prion protein changes its infectious properties -- including the prion's ability to jump "species barriers."

The research, based on studies of prion infectivity in yeast, solves one of the great puzzles about prions: If they are infectious proteins with no genetic material of their own and no ability to mutate genetically, how can a single prion exist in different strains that can cause different diseases? The puzzle has led some to doubt that a protein alone causes mad cow and related diseases.

To reconcile the existence of prion strains with the "protein-only" hypothesis of prion propagation, scientists had proposed that a single protein can misfold into multiple different infectious conformations: one for each different type of prion strain.

The new finding confirms this view. It shows that shape change accounts for strain differences, and it lays the groundwork for research to determine the physical differences that allow a prion to change shape and cause different diseases. Answers could lead to strategies to block the folding or its route to disease, the scientists say.

The UCSF discovery is published in the March 18 issue of Nature. A second paper in the same issue of the journal by scientists at Florida State University reaches similar conclusions.

A News and Views commentary in Nature on the two research findings concludes that the work firmly establishes the link between different prion forms and different prion strains.

A prion is thought to cause disease by inducing other proteins to adopt its contorted shape and form sheets called amyloids. UCSF's Stanley Prusiner, MD, received the 1997 Nobel Prize in Physiology or Medicine for the discovery of prions and the underlying principles of their mode of action.

Different strains of the mammalian prion play important roles in determining the degree to
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Contact: Wallace Ravven
wravven@pubaff.ucsf.edu
415-476-2557
University of California - San Francisco
17-Mar-2004


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