Figure 2: The spatial relationship of epitopes on the HIV-1 gp120 glycoprotein.

a, The molecular surface of the gp120 core is shown, using the same perspective as in Fig. 1a. The modelled N-terminal gp120 core residues, V4 loop and carbohydrate structures are included. The variability of the molecular surface is indicated (colour scheme as in Fig. 1b). The modelled carbohydrates are shown in light blue (complex sugars) or dark blue (high-mannose sugars). The approximate locations of the V2 and V3 variable loops are indicated. Note the well-conserved surfaces near the ‘Phe 43’ cavity and the chemokine-receptor-binding site (Fig. 1a). b, Cα tracing of the gp120 core, oriented as in Fig. 1a. The gp120 residues within 4 Å of the 17b CD4i antibody are shown in green; those implicated in the binding of CD4BS antibodies²² are in red. Changes in these residues significantly affect the binding of at least 25% of the CD4BS antibodies listed in Table 1. The residues implicated in 2G12 binding¹⁹ are shown in blue. The V4 variable loop, which contributes to the 2G12 epitope¹⁹, is indicated by dotted lines. c, The molecular surface of the gp120 core, oriented and coloured as in b. d, Approximate locations of the faces of the gp120 core, defined by the interaction of gp120 and antibodies. The molecular surface accessible to neutralizing ligands (CD4 and CD4BS, CD4i and 2G12 antibodies) is shown in white. The neutralizing face of the complete gp120 glycoprotein includes the V2 and V3 loops, which are found adjacent to the surface shown (a). The approximate location of the gp120 face that is poorly accessible on the assembled envelope glycoprotein trimer and therefore elicits only non-neutralizing antibodies⁵,⁶ is shown in magenta. The approximate location of an immunologically ‘silent’ face of gp120, which roughly corresponds to the highly glycosylated outer domain surface, is in blue.