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Scripps research scientists determine structure of immune molecule that counteracts HIV strains
Date:6/1/2010

and kill the virus.

Most of the antibodies that the body produces to fight HIV, however, are ineffective. The surface of the virus is cloaked with sugar molecules that prevent antibodies from slipping in and blocking the proteins the virus uses to latch onto a cell and infect it. To make matters more complicated, HIV is constantly mutating, so there are multiple HIV strains that antibodies elicited in any vaccine must be able to sense and destroy.

Nonetheless, while rare, broadly neutralizing antibodies against HIV do exist.

Last year, a team of scientists from IAVI, Scripps Research, Theraclone Sciences, and Monogram Biosciences published research from a systematic search for such antibodies among 2,000 volunteers. The study revealed two powerful new broadly neutralizing antibodies against HIVPG9 and PG16, isolated from a volunteer in Africa.

"Hammerhead" Structure

Once the broadly neutralizing antibodies were discovered, the next challenge was to figure out how they worked. To shed light on this question, in the current study members of the Wilson lab turned to x-ray crystallography, a technique that can solve structures to exquisitely high resolution.

In x-ray crystallography, scientists manipulate a protein or some other molecule so that a crystal forms. This crystal is then placed in front of a beam of x-rays, which diffract when they strike the atoms in the crystal. Based on the pattern of diffraction, scientists can reconstruct the shape of the original molecule. The scientists succeeded in forming crystals of the active part of the PG16 antibody, and in reconstructing the structure from the datawith some surprising results.

"The antibody has a novel and really interesting subdomain that hasn't been seen before," said Research Associate Rob Pejchal, who is first author of the paper. "This subdomain, which we found plays a major role in the recognition and neutralization of HIV, has a dif
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Contact: Keith McKeown
kmckeown@scripps.edu
858-784-8134
Scripps Research Institute
Source:Eurekalert

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