HIV GLYCOPROTEIN STRUCTURE

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. HIV-1 envelope glycoprotein (gp120/gp41) plays a critical role in virus infection and pathogenesis. Three of the six monoclonal antibodies (mAbs) considered to have broadly neutralizing activities (2F5, 4E10, Z13e1) bind to the membrane proximal external region (MPER) of gp41. This makes the MPER a desirable template for developing immunogens that can elicit antibodies with properties similar to these mAbs, with a long-term goal of developing antigens that could serve as novel HIV vaccines. In order to provide a structural basis for rational antigen design, an MPER construct, HR1-54Q, was generated for x-ray crystallographic study to provide high-resolution atomic coordinates. The structure will most likely represents a post-fusion form of gp41 and we hope that the structure will provide a rational basis for gp41 antigen design suitable for HIV vaccine development.