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Researchers reveal insights into hidden world of protein folding
Date:6/11/2008

The proteins upon which life depends share an attribute with paper airplanes: Unless folded properly, they just won't fly.

But researchers have been puzzled by how the long, linear proteins cranked out by the ribosome factories in a cell are folded into the shapes they must assume to perform their function. They only have known that for many of the most complex and essential proteins, the folding takes place out of sight, hidden in the inner cavity of a type of molecule called a chaperonin.

Now Stanford researchers have begun prying open the lid, literally, on the inner workings of chaperonin molecules by deducing the mechanism by which the lid operates on a barrel-shaped chaperonin called TRiC.

"Understanding how the lid opens and closes really helps us understand how everything moves inside the chaperonin," said Judith Frydman, associate professor of biology and one of two senior authors of a paper published online this week in Nature Structural & Molecular Biology.

"This is just the beginning, but now we can start to understand how the protein is pushed inside the cavity of the chaperonin and what this folding chamber looks like," Frydman said. Learning how a protein is manipulated inside TRiC while it is being folded is a crucial step in Frydman's larger plan.

"Our goal is to eventually exert control," she said. "If we could re-engineer the chaperonin to either fold better misfolded proteins or alternatively to remove them from circulation, then we could prevent those proteins from being harmful to cells."

Misfolded proteins have been implicated in a number of diseases, including some cancers, as well as ailments related to aging, such as Alzheimer's and Parkinson's diseases.

"Folding is one of the key steps for the health of the cell," Frydman said.

Virtually all proteins have to be folded-some in complex configurations-in order to function properly, and many are known to requir
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Contact: Louis Bergeron
louisb3@stanford.edu
650-725-1944
Stanford University
Source:Eurekalert

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