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A trimeric structural domain of the HIV-1 transmembrane glycoprotein

Abstract

Infection with HIV-1 is initiated by fusion of cellular and viral membranes. The gp41 subunit of the HIV-1 envelope plays a major role in this 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 ectodomain. In isolation, N-51 is predominantly aggregated and C-43 is unfolded. When mixed, however, these peptides associate to form a stable, α-helical, discrete trimer of heterodimers. Proteolysis experiments 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 interior, parallel, homotrimeric, coiled-coil core, against which three C-43 helices pack in an antiparallel fashion. We suggest that this α-helical, trimeric complex is the core of the fusion-competent state of the HIV-1 envelope.

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Lu, M., Blacklow, S. & Kim, P. A trimeric structural domain of the HIV-1 transmembrane glycoprotein. Nat Struct Mol Biol 2, 1075–1082 (1995). https://doi.org/10.1038/nsb1295-1075

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