The HIV/1 envelope glycoproteins gp120 and gp41 initiate infection by mediating the attachment of virus particles to cell-surface CD4 receptors in association with chemokine receptors. The long-term objective of this work is to understand the structure and function of the gp4l transmembrane protein by solving its protein crystal structure and mapping epitopes of neutralizing MoAbs raised against the functionally active form. Since many retroviral transmembrane proteins are thought to share similar features, large fragments of the ectodomains of the transmembrane proteins (TM) of HIV-1, HIV-2, FIV and HTLV-1 have been expressed for crystallization trials. Crystals of the TM fragments of HIV-2, FIV and HTLV-1 have been obtained, with the HTLV-1 crystals suitable for diffraction studies. Efforts have been concentrated expressing forms of the TM proteins that oligomerize and resemble the native structure as well, because it is known that monoclonal antibodies that bind to the oligomeric envelope complex exhibit better neutralizing activity than those that bind to monomeric species. It is hoped that solving the gp4l structure will shed light on its immune recognition and how it functions in the fusion process during infection. This information could provide clues for vaccine development and small molecule drug design.
