The Dragon protein

[Guest guest]

Interesting article about the discovery of a dragon-shaped protein

complex in H5N1 that is critical to its reproduction and the various

ways it might stifled, including putting a " bit " in the dragon's jaws!

http://www.eurekalert.org/pub_releases/2008-07/dnl-nd071508.php

Newly described 'dragon' protein could be key to bird flu cure

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 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. "

Joachimiak hopes to more precisely identify the types of compounds

that could inhibit RNA replication in H5N1 by looking at the

atomic-level grooves and pockets within the PA " mouth " region.

According to Joachimiak, scientists must gain a more thorough

understanding of the geometry of that small region in order to

effectively synthesize drugs that could prevent the further spread of

bird flu.

###

Argonne researchers Joachimiak and Rongguang Zhang collaborated with

Zihe Rao and Yingfang Liu, both members of the Institute of Biophysics

of Chinese Academy of Sciences. Rao is one of the most influential

Chinese crystallographers and biophysicists, Joachimiak said. The

protein samples were manufactured in China and crystals were shipped

to Argonne for data collection and structural analysis.

The results of the study will be reported in an upcoming issue of

Nature and can be found online at

http://dx.doi.org/10.1038/nature07120. The work was funded by the

National Natural Science Foundation of China as well as the Chinese

Ministry of Science and Technology and the U.S. Department of Energy's

Office of Biological and Environmental Research.

About Argonne

The U.S. Department of Energy's Argonne National Laboratory brings the

world's brightest scientists and engineers together to find exciting

and creative new solutions to pressing national problems in science

and technology. The nation's first national laboratory, Argonne

conducts leading-edge basic and applied scientific research in

virtually every scientific discipline. Argonne researchers work

closely with researchers from hundreds of companies, universities, and

federal, state and municipal agencies to help them solve their

specific problems, advance America's scientific leadership and prepare

the nation for a better future. With employees from more than 60

nations, Argonne is managed by UChicago Argonne, LLC for the U.S.

Department of Energy's Office of Science.