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Picturing Prions


By Jessa Forte NettingSeptember 9, 2005 5:00 AM


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Working independently, three teams of researchers have developed a clear picture of the structure and mechanism of the misshapen, threadlike proteins—called prions in their infectious form—that are the hallmarks of mad cow disease, Alzheimer’s, Parkinson’s, and 19 other brain-wasting diseases.

Scientists have long suspected that something about the prions’ shape makes them infectious. In the communicable Creutzfeldt-Jakob disease (mad cow in humans), the unusual filaments build up into clumps inside cells. Earlier studies gave only hazy images of their structure. “Proteins are the machines of the body and of pathogens,” says David Eisenberg of UCLA. “To interfere with them we have to be able to see them and how they work together—just as you would if you tried to fix a car.”

Using three complementary approaches, the groups took different snapshots of the prions’ mechanics. One team, from the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts, found that when proteins form a disorganized goo, they can foster the creation of filaments.

Meanwhile, Eisenberg and his group zoomed in on a yeast prion, discovering that it had interlocking teeth like a zipper, which contorted the proteins into a ropelike shape. Unlike a zipper, however, once closed, the prion can’t reopen. A third international team showed that the core of this zipper drives infections, converting other proteins.

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