( Researchers have known for decades that...)Scientists identify prion's infectious secret

Researchers have known for decades that certain neurodegenerative diseases, such as mad cow disease or its human equivalent, Cruetzfeldt-Jakob disease, result from a kind of infectious protein called a prion. Remarkably, in recent years researchers also have discovered non-pathogenic prions that play beneficial roles in biology, and prions even may act as essential elements in learning and memory.

But although prions have received a great deal of scrutiny, scientists still don’t understand many of the most fundamental mechanisms of how prions form, replicate and cross from one species to another.

Now, through studying non-toxic yeast prions, scientists at Whitehead Institute have discovered small but critical regions within prions that determine much of their behavior.

"These findings provide a new framework for us to begin exploring properties of prion biology that, up until now, have proven difficult to investigate," says Whitehead Member and MIT Professor of Biology Susan Lindquist, senior author on the paper, which will appear in the May 9 online issue of Nature.

Proteins are the cell’s workhorses, and they need to fold into complex and precise shapes to do their jobs. Prions are proteins that start out normally, but then at some point misfold—rather like an origami swan that comes out looking and acting instead like a vulture.

But prions have another characteristic that enables them to wreak havoc. They recruit other, properly folded proteins into misforming along with them, a process Lindquist calls a "conformational cascade." In many organisms, this conformational cascade creates long fibers called amyloids. (The brains of animals that have died from prion infections are literally packed with amyloid clumps.)

In order to glean insights into the mechanics that enable amyloid formation, Peter Tessier, a postdoctoral scientist in Lindquist’s lab, used peptide arrays—glass slides covered with thousands
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Source:Whitehead Institute for Biomedical Research

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