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Newly described 'dragon' protein could be key to bird flu cure
Date:7/15/2008

ARGONNE, Ill. (July 15, 2008) -- Scientists and researchers have taken a big step closer to a cure for the most common strain of avian influenza, or "bird flu," the potential pandemic that has claimed more than 200 lives and infected nearly 400 people in 14 countries since it was identified in 2003.

Researchers at the U.S. Department of Energy's (DOE) Argonne National Laboratory, in conjunction with scientists from China and Singapore, have crystallized and characterized the structure of one of the most important protein complexes of the H5N1 virus, the most common strain of bird flu.

All viruses, including H5N1, contain only a small number of proteins that govern all of the viruses' functions. In H5N1, perhaps the most important of these proteins is RNA polymerase, which contains the instructions that allows the virus to copy itself along with all of its genetic material. The Argonne study focused on H5N1's RNA polymerase protein, which contains three subunits: PA, PB1 and PB2.

After performing X-ray crystallography on the protein crystals at Argonne's Structural Biology Center 19ID beamline at the Advanced Photon Source, the researchers saw a surprising resemblance in the protein structure's image. "When we mapped out the PA subunit, it looked very much like the head of a dragon," said Argonne biophysicist Andrzej Joachimiak. "One domain looked like the dragon's brains, and the other looked like its mouth."

During RNA replication the phase during which the virus "reproduces" all three of the subunits of the protein assemble themselves in a particular configuration. In order for this congregation to take place, the researchers determined the end of the PB1 subunit has to insert itself and bind to the "dragon's mouth" part of the PA subunit.

This unexpected relationship between the two subunits could inspire a number of different therapies or vaccines for H5N1 that rely on muzzling the "dragon's" jaws with
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Contact: Steve McGregor
smcgregor@anl.gov
630-252-5580
DOE/Argonne National Laboratory
Source:Eurekalert

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