Figure 1: Structure and orientation of the HIV-1 gp120 core.

a, A Cα tracing of the gp120 core, which was crystallized in a ternary complex with two-domain soluble CD4 and the Fab fragment of the 17b antibody¹², is shown. The gp120 core is seen from the perspective of CD4, and is oriented with the viral membrane at the top of the figure and the target cell membrane at the bottom. The inner gp120 domain is shown in red and the outer domain in yellow; the ‘bridging sheet’ is orange. The N and C termini of the truncated gp120 core are labelled, as are the positions of structures related to the gp120 variable regions V1–V5. The ℒA, ℒC, ℒD and ℒE surface loops¹² are shown. The position of the Phe 43 cavity involved in CD4 binding is indicated by an asterisk. The gp120 surface implicated in binding to the CCR5 chemokine receptor (C. Rizzuto and J.G.S., submitted) is shown. The perspectives shown in b–d are indicated. b, View of the molecular surface of the gp120 outer domain, from the perspective indicated in a. The molecular surface on the left is coloured according to the variability observed in gp120 residues among primate immunodeficiency viruses: red, residues conserved among all primate immunodeficiency viruses; orange, residues conserved in all HIV-1 isolates; yellow, residues exhibiting some variation among HIV-1 isolates; and green, residues showing significant variability among HIV-1 isolates (see Methods). The variability of the gp120 surface is underestimated here because the V4 variable loop, which is not resolved in the structure, contributes to this surface (approximate location is indicated). The position of the V5 region is shown. Also note the highly conserved glycosylation site (Asn 356 and Thr/Ser 358) within the ℒE loop, between the V5 and V4 regions. On the right, the V4 loop and the carbohydrates are modelled (see Methods). The complex carbohydrate addition sites used in mammalian cells¹⁴ are coloured light blue, and the high-mannose sites are dark blue. The gp120 protein surface is in white. c, View of the gp120 molecular surface that faces the target cell. Variability is indicated on the left, using the same colour scheme as in b. Note the clear demarcation between the conserved surface, which has been implicated in the formation of CD4i epitopes¹⁸ and in chemokine-receptor binding (C. Rizzuto and J.G.S., submitted), and the variable surface of the outer domain. The recessed binding site for CD4 is indicated, flanked by the V1/V2 stem, which is labelled. The V4 loop and the carbohydrates are modelled on the right (colouring as in b). Particular carbohydrates referred to in the text are labelled. d, View of the molecular surface of the gp120 core inner domain. Variability is indicated on the left by the colour scheme used in b. The CD4-binding site is on the right; the protruding V1/V2 stem is indicated. The conserved molecular surface, which is associated with the inner domain of the gp120 core, is devoid of known N-linked glycosylation sites. These are modelled on the right, which is coloured as in b.