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UCSD discovery may provide novel method to generate medically useful proteins

A team led by University of California, San Diego biochemists has discovered the mechanism by which a simple organism can produce 10 trillion varieties of a single protein, a finding that provides a new tool to develop novel drugs.

In the September 18 advance on-line publication of the journal Nature Structural and Molecular Biology, the researchers describe the mechanism by which a virus that infects bacteria--called a bacteriophage, or phage--can generate a kaleidoscope of variants of a particular protein. The paper will appear in print in Nature Structural and Molecular Biology in October.

Since this degree of protein diversity is extremely rare, recreating the process in a test tube could give researchers a new way to generate therapeutic enzymes, vaccines and other medically important proteins.

"This is only the second type of massively variable protein ever discovered," explained Partho Ghosh, a professor of chemistry and biochemistry at UCSD who headed the research team. "Only antibodies have more variation than this protein in phage. However, the genetic mechanism used by the phage to generate this diversity is completely different from that used by animals to produce antibodies, and has the advantage of giving the protein greater stability." "If we can learn from these organisms how to set up a system that churns out proteins with enormous variability, it may be possible to target these new proteins to specific cells to treat disease," said Stephen McMahon, a former postdoctoral fellow in Ghosh's lab who conducted much of the research. "This idea has already been picked up by the biotech industry."

The function of the massively variable phage protein is to tether the phage to the bacteria they infect. The phage "predator" protein fits into a "prey" protein on the bacteria like a three-dimensional puzzle piece. However, the bacteria are constantly changing the proteins on their surface. To keep up with the unpr
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Contact: Sherry Seethaler
sseethaler@ucsd.edu
858-534-4656
University of California - San Diego
18-Sep-2005


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