http://www.boston.com/news/daily/02/proteins.htm

Researchers get first images of rogue proteins suspected in mad cow and other diseases

By Associated Press, 09/02/01

CLEVELAND -- Researchers have captured the first images of a type of human protein called prions, paired up in a way that might lead to "mad cow" and other diseases.

The proteins are molecules that scientists had thought normally exist alone. Pictures taken by Cleveland Clinic and Case Western Reserve University scientists show a pair of prions linked.

Several research teams worldwide have been trying to figure out how normal, harmless prions change into the deadly mad cow variety, which destroys brain tissue, and how they accumulate in clumps. The prion-to-prion link, which the Cleveland researchers pictured, may be an intermediate step in the processes.

"This is the first time anyone's seen an in-between" stage, said Vivien Yee of the Cleveland Clinic. She led the imaging effort with Witold Surewicz of the Case Western Reserve University medical school.

Knowing that prions can link could lead to tests to detect the beginnings of prion-related diseases and the search for drugs to halt the pairing.

The findings, which included work by Cleveland State University, will be published this week in the journal Nature Structural Biology.

"It's very interesting research which uncovers a new aspect of the prion protein," said David Eisenberg, who works in the structural biology field at the University of California at Los Angeles.

The Cleveland team used a powerful imaging technique called X-ray crystallography to capture the images.

First, they obtained prions by putting a human gene that carries prion-making instructions into a simple bacteria, which churned out copies.

They were lucky in this early stage to have a linked pair of prions in one of the samples, although they didn't know that until much later.

After coaxing the prion proteins into forming crystals, they bombarded them with X-rays. Computers recorded the echoes of the radiation bouncing off the clouds of electrons that surround the prions' atoms, then used the data to construct a rough outline of the prion's atomic architecture.

It "gives us a kind of image so we can really visualize some events that before were nebulous," said Pierluigi Gambetti, a Case neuropathologist who directs a national prion disease surveillance center and is working to design a fast screening test for mad cow disease, or bovine spongiform encephalopathy.

-- Anonymous, September 02, 2001