"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 Ward, who is an assistant professor in TSRI's Department of Integrative Structural and Computational Biology.
In the current work the Weill Cornell-TSRI team was able to engineer a version of the Env trimer (three-component structure) that has the stability and other properties needed for atomic-resolution imaging, yet retains virtually all the structures found on native Env.
Using cutting-edge imaging methods, electron microscopy (spearheaded by graduate student Dmitry Lyumkis) and X-ray crystallography (led by Jean-Philippe Julien, a senior research associate in the Wilson lab), the team was then able to look at the new Env trimer. The X-ray crystallography study was the first ever of an Env trimer, and both methods resolved the trimer structure to a finer level of detail than has been reported before.
The data illuminated the complex process by which the Env trimer assembles and later undergoes radical shape changes during infection and clarified how it compares to envelope proteins on other dangerous viruses, such as flu and Ebola.
"It has been a privilege for us to work with the Scripps team on this project," said Moore on behalf of the Weill Cornell group. "Now we all need to harness this new knowledge to design and test next-generation trimers and see if we can induce the broadly active neutralizing antibodies an effective vaccine is going to need."
Other contributors to the studies, "Cryo-EM structure of a fully glycosylated soluble cleaved HIV-1 envelope trimer," and "Crystal structure of a soluble cleaved HIV-1 envelope trimer," included TSRI
|SOURCE The Scripps Research Institute|
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