Scientists determine atomic-level structure of key HIV protein

Researchers determined the first atomic-level structure of the tripartite HIV envelope protein, which was long thought to be one of the most difficult targets in structural biology, The Scripps Research Institute said on Thursday.

Collaborating scientists at TSRI and Weill Cornell Medical College determined the structure for the protein, which is so complex and delicate that prior scientists had difficulty obtaining the protein in a suitable form for atomic-resolution imaging. The scientists engineered a version of the protein with the stability and other properties needed for the imaging. The researchers then used cutting-edge imaging methods, electron microscopy and X-ray crystallography to look see the atomic-level structure of the envelope protein, known as Env.

The findings provide the most detailed picture yet of the HIV's complex envelope, including sites that could be targeted by future vaccines.

"Most of the prior structural studies of this envelope complex focused on individual subunits; but we've needed the structure of the full complex to properly define the sites of vulnerability that could be targeted, for example with a vaccine," Ian Wilson, a senior author of the new research, said.

The data highlighted the complex process by which the Env three-component structure assembles and undergoes dramatic shape changes during infection. The imaging clarified how the Env trimer compares to envelope proteins on other dangerous viruses, like Ebola and flu.

"It has been a privilege for us to work with the Scripps team on this project," John Moore, a senior author of the research with Weill Cornell, said. "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."

The researchers published the findings in two papers in Science Express on Thursday.