The Stanford group also weighed in on another controversy concerning the actual mechanism that allows RNAP to advance. "RNAP is a molecular motor that starts at one end of the DNA and walks down to the other end," Block explains. "It gets its energy from the chemical reaction that occurs when it copies A, T, G or C. It's as if a machine that lays down asphalt could somehow be powered by the asphalt itself."

Scientists have come up with two different models to explain what drives this molecular motor:

• The power stroke model, in which pent up energy thrusts the enzyme forward--like a loaded spring that's periodically released.
• The Brownian (or thermal) ratchet model, whereby random thermal energy causes the RNAP enzyme to jiggle back and forth. Each incoming DNA base then locks the enzyme into the forward position so that it cannot jiggle backwards. "It would be as if you were repeatedly bouncing off a wall, and every time you happened to bounce a bit farther away, somebody came in and moved the wall up behind you, so you couldn't bounce so far back. You'd wind up drifting forwards, even though your own motion was mostly random," Block explains.

In the Nature study, Block and his colleagues concluded that the Brownian ratchet model is probably correct for RNAP, even though several other motor proteins are believed to move instead by the power stroke mechanism. "We've certainly come down hard in favor of the Brownian ratchet camp and against the power stroke camp," Block says. "But does that mean all power stroke models have been ruled out and that all Brownian ratchet models are acceptable? No."

Molecular folding

The Block team also applied the new force clamp technology to one the hottest fields in biomedical research--molecular folding. For a protein to function properly, it has to fold into a specific, intricate three-dimensional shape. Diseases such as Alzheimer's, Mad Cow and P
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Contact: Mark Shwartz
mshwartz@stanford.edu
650-723-9296
Stanford University
13-Nov-2005