‘Dragon’ protein could be key to bird flu cure

July 17th, 2008 - 1:36 pm ICT by IANS  

Washington, July 17 (IANS) Scientists are edging closer to a cure for the commonest strain of bird flu, one that has killed more than 200 people and infected 400 people in 14 countries since its identification in 2003. US Department of Energy’s researchers, along with scientists from China and Singapore, have crystallised the structure of important protein complexes of the H5N1 virus, the bird flu strain.

In H5N1, the most important of these proteins is thought to be RNA polymerase, which contains the instructions that allows the virus to copy itself along with all of its genetic material.

Researchers focussed on H5N1’s RNA polymerase protein, which contains three subunits: PA, PB1 and PB2. After performing X-ray crystallography on protein crystals at Argonne’s Structural Biology Centre, 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 at which 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 another molecule or chemical compound that would block the PB1 subunit’s access to the PA site, according to Joachimiak.

“If we can put a bit in the dragon’s mouth, we can slow or even potentially someday stop the spread of avian flu,” he said. “Since we are talking about a relatively small protein surface area, finding a way to inhibit RNA replication in H5N1 seems very feasible.”

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