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Protein fishing in America: The movie

PHILADELPHIA--Proteins pass messages to other proteins much like fly-fishermen flicker their lines against water, or so a current leading theory holds. The repeated weak slapping of protein surfaces against one-another is the critical first step in a chain of events that rule all subsequent cellular behavior.

But this vital exchange between single molecules has defied direct observation because that line-flicking and message-passing happen randomly at such a small scale.

A Pacific Northwest National Laboratory team led by H. Peter Lu, using a technique called single-molecule photon stamping spectroscopy, has now observed real-time interactions of single proteins. Their experimental evidence, reported Thursday at the 228th national meeting of the American Chemical Society, supports the fly-fishing theory of protein communication.

"In the past five years, the field of protein-protein interaction dynamics has exploded," said Lu, a staff scientist at the Department of Energy laboratory in Richland, Wash. "Measurements to date have been snapshots of proteins. But to do dynamic measurements, to capture proteins in motion, this is unique."

Techniques such as nuclear magnetic resonance and x-ray crystallography reveal structural details about proteins and positions of their atoms at a particular time in space. They provide structural reference points, but to contrive interactions, many images have to be gathered at different times, events averaged out and a narrative flow imposed. The effect is akin to cutting a cartoon into a thousand frames tossing the pieces from the ceiling like confetti, then gathering them off the floor and reassembling them. Try making sense of that.

"It's not an observation in real time," Lu said. "You're measuring many proteins at a time, and you get information about two states and two states only: binding or not binding. How the binding and not binding are linked is hidden information." Lu's single-molec
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Contact: Bill Cannon
cannon@pnl.gov
509-375-3732
DOE/Pacific Northwest National Laboratory
26-Aug-2004


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