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Unprecedented view of protein folding may help develop brain disease therapies
Date:3/15/2011

e aperture has closed. A paper describing their findings was published earlier this year in Cell.

Frydman said there were two likely ways in which a protein, initially a linear chain of molecules (amino acids), could theoretically be folded inside the chamber.

One is by mechanical means, with the chamber holding onto the protein and physically pushing it into the right shape.

"The other one is that when the lid closes, the chaperonin lets go of the protein, but some special chemical properties in this chamber somehow make it fold," she said. "Our evidence is that this mechanism is the correct one."

The only way to know which mechanism was doing the work was to see inside the chamber while the folding was happening, but simply opening up the lid wouldn't work, because the shape of the entire chamber changes in accordance with the motion of the lid. When the lid spirals open, the walls of the chamber spiral open, too, and the protein floats away.

To see what was happening, Frydman's team devised a chemical "trick" by which they could remove the lid on the chamber, but still get the walls of the chamber to close in, as if the lid were spiraling.

When they "closed" the lidless chamber, the chaperonin simply released the protein that had been destined to be folded. Like a long balloon that slipped from a child's grip before it could be folded into a giraffe, the protein simply drifted off.

The challenge then became figuring out how the protein was getting released.

"One of the reasons why the mechanical model of pushing the protein into shape without letting go had been proposed was because there was no obvious way for this chaperonin to let go of the protein," Frydman said.

When a protein gets grabbed for folding by TRiC, it is held by eight binding sites along the walls of the chamber. Between each binding site is a tiny loop. Frydman's team suspected that during the closing process
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Contact: Louis Bergeron
louisb3@stanford.edu
650-725-1944
Stanford University
Source:Eurekalert  

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