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Scientists capture most detailed picture yet of key AIDS protein
Date:10/31/2013

s with a stalk-like subunit, gp41, and a cap-like region, gp120. Each trimer resembles a mushroom and about 15 of these Env trimers sprout from the membrane of a typical virus particle, ready to latch onto susceptible human cells and facilitate viral entry.

Although Env in principle is exposed to the immune system, in practice it has evolved highly effective strategies for evading immune attack. It frequently mutates its outermost "variable loop" regions, for example, and also coats its surfaces with hard-to-grip sugar molecules called glycans.

Even so, HIV vaccine designers might have succeeded by now had they been able to study the structure of the entire Env protein at atomic-scale--in particular, to fully characterize the sites where the most effective virus-neutralizing antibodies bind. But Env's structure is so complex and delicate that scientists have had great difficulty obtaining the protein in a form that is suitable for atomic-resolution imaging.

"It tends to fall apart, for example, even when it's on the surface of the virus, so to study it we have to engineer it to be more stable," said Dr. Ward, who is an assistant professor in TSRI's Department of Integrative Structural and Computational Biology. The key goal in this area has been to engineer a version of the Env trimer that has the stability and other properties needed for atomic-resolution imaging, yet retains virtually all of the complex structural characteristics of native Env.

Imaging Env

After many years in pursuit of this goal, Drs. Moore, Rogier W. Sanders and their colleagues at Weill Cornell, working with Drs. Wilson, Ward and others at TSRI, recently managed to produce a version of the Env trimer (called BG505 SOSIP.664 gp140) that is suitable for atomic-level imaging work--and includes all of the trimer structure that normally sits outside the viral membrane. The TSRI researchers then evaluated the new Env trimer using advanced versions
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Contact: Sarah Smith
sas2072@med.cornell.edu
646-317-7401
Weill Cornell Medical College
Source:Eurekalert

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