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Nano mechanism to control protein may lead to new protein engineering

UCLA scientists have created a mechanism at the nanoscale to externally control the function and action of a protein.

"We can switch a protein on and off, and while we have controlled a specific protein, we believe our approach will work with virtually any protein," said Giovanni Zocchi, assistant professor of physics at UCLA, member of the California NanoSystems Institute and leader of the research effort. "This research has the potential to start a new approach to protein engineering."

The research, published in the journal Physical Review Letters, potentially could lead to a new generation of targeted "smart" pharmaceutical drugs that are active only in cells where a certain gene is expressed, or a certain DNA sequence is present, Zocchi said. Such drugs would have reduced side effects. The research, federally funded by the National Science Foundation, also may lead to a deeper understanding of proteins' molecular architecture.

Proteins are switched on and off in living cells by a mechanism called allosteric control; proteins are regulated by other molecules that bind to their surface, inducing a change of conformation, or distortion in the shape, of the protein, making the protein either active or inactive, Zocchi explained.

"We have made an artificial mechanism of allosteric control based on mechanical tension -- the first time this has ever been done," Zocchi said. "Potentially, the applications could be very far-reaching and beneficial if the research continues to progress well.

"We insert a molecular spring on the protein, and we can control the stiffness of the spring externally," he said. "We chemically string a short piece of DNA around the protein. We can switch the protein on and off by changing the stiffness of the DNA. We have made a new molecule, which we can control. By gluing together two disparate pieces of the cell's molecular machinery, a protein and a piece of DNA, we have created a spring-loaded protein
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Contact: Harlan Lebo
hlebo@college.ucla.edu
310-206-0511
University of California - Los Angeles
15-Feb-2005


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