ATOMIC-STRUCTURE OF THE ECTODOMAIN FROM HIV-1 GP41

Fusion of viral and cellular membranes by the envelope glycoprotein gp 120/gp41 effects entry of HIV-1 into the cell. The precursor, gp160, i s cleaved post-translationally into gp120 and gp41 (refs 1, 2), which remain non-covalently associated. Binding to both CD4 and a co-recepto r leads to the conformational changes in gp120/gp41 needed for membran e fusion(3). We used X-ray crystallography to determine the structure of the protease-resistant part(4,5) of a gp41 ectodomain solubilized w ith a trimeric GCN4 coiled coil in place of the amino-terminal fusion peptide(6). The core of the molecule is found to be an extended, tripl e-stranded alpha-helical coiled coil with the amino terminus at its ti p. A carboxy-terminal alpha-helix packs in the reverse direction again st the outside of the coiled coil, placing the amino and carboxy termi ni near each other at one end of the long rod. These features, and the existence of a similar reversal of chain direction in the fusion pH-i nduced conformation of influenza virus HA2 (ref. 7) and in the transme mbrane subunit of Moloney murine leukaemia virus(8) (Fig. 1a-d), sugge st a common mechanism for initiating fusion.