Structure of clade C HIV-1 envelope glycoprotein determined

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Researchers at the Scripps Research Institute (CA, USA) have demonstrated the structure of a HIV-surface protein and designed a mimic of this viral protein that could be utilized in a candidate HIV vaccine.

Previously, research has produced high-resolution structures for the envelope glycoproteins of HIV-1 subtypes clade A, B and G. The glycoprotein from clade C is notoriously unstable,however, with clade C responsible for the majority of infections worldwide, a high-resolution structure is critical.

In this study, the team re-engineered the structure of the HIV envelope glycoprotein to generate a stabilized, soluble clade C protein, as first author Javier Guenaga (Scripps Research Institute) explained: “We reinforced the structure to get the soluble molecule to assemble as it is on the viral surface.”

This process allowed the scientists to determine the envelope glycoprotein’s crystal structure to 3.9 Å, however, there were many challenges to overcome. Author Fernando Garces (Scripps Research Institute) commented:  “Despite all the engineering employed to produce a stable clade C protein, these crystals (of clade C protein) were grown in very challenging conditions at 4 degrees Celsius and it took the diffraction of multiple crystals to generate a complete dataset, as they showed high sensitivity to radiation damage. Altogether, this highlights the tremendous effort made by the team in order to make available the molecular architecture of this very important immunogen.”

The study, which was published recently in Immunity, was accompanied by a second study from scientists at the Karolinska Institute in Stockholm (Sweden), who demonstrated that the immunogen uncovered by the Scripps scientists can elicit neutralizing antibodies in non-human primates.

Guenaga stated: “That was great to see, this study showed that the immunogens we made are not artificial molecules—these are actually relevant for protecting against HIV in the real world.”

Lead author Richard Wyatt (Scripps Research Institute) added: “Together, the two studies reiterate how structure-based immunogen design can advance vaccine development.”

The redesigned protein permits the generation of immunogens from a variety of clades, and the results are now part of growing library of immunogens, with the potential to be incorporated into vaccine.

Author, Ian Wilson, form the Scripps Research Institute, concluded: “All of this research is going toward finding combinations of immunogens to aid in protecting people against HIV infection.”

Sources: Guenaga J, Garces F, de Val N et al. Glycine Substitution at Helix-to-Coil Transitions Facilitates the Structural Determination of a Stabilized Subtype C HIV Envelope Glycoprotein. Immunity. doi:10.1016/j.immuni.2017.04.014 (2017) (Epub ahead of print); www.scripps.edu/news/press/2017/20170526wyatt_wilson.html

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