A TRIMERIC STRUCTURAL DOMAIN OF THE HIV-1 TRANSMEMBRANE GLYCOPROTEIN

Infection with HIV-1 is initiated by fusion of cellular and viral memb ranes. The gp41 subunit of the HIV-1 envelope plays a major role in th is process, but the structure of gp41 is unknown, We have identified a stable, proteinase-resistant structure comprising two peptides, N-51 and C-43, derived from a recombinant protein fragment of the gp41 ecto domain. In isolation, N-51 is predominantly aggregated and C-43 is unf olded. When mixed, however, these peptides associate to form a stable, alpha-helical, discrete trimer of heterodimers. Proteolysis experimen ts indicate that the relative orientation of the N-51 and C-43 helices in the complex is antiparallel. We propose that N-51 forms an interio r, parallel, homotrimeric, coiled-coil core, against which three C-43 helices pack in an antiparallel fashion. We suggest that this alpha-he lical, trimeric complex is the core of the fusion-competent state of t he HIV-1 envelope.