Crystal structure of an HIV-binding recombinant fragment of human CD4 - PubMed (original) (raw)

FIG. 5

Images of CD4 relating to sites of interaction with HIV. a, C_α_ backbone of D1 with sites implicated by mutational and structural analysis to affect high-affinity gp120 binding (see Table 2). Non-buried residues that show reduction in binding without global disruption of structure (as judged by antibody binding) are coloured red-orange (29, 41, 42, 43, 44, 45, 47, 49, 52, 58, 59, 77, 81 and 85) on a backbone drawn by WORM (L. Andrews). The orientation is as in Figs 2 and 3. b, Van der Waals’ surface of D1 with side chains of gp120-sensitive residues coloured. Those showing marked reductions are in pink (43, 44, 85, are visible) and those showing moderate effects are in purple (59, 42, are visible). The point of view is from above a, looking down at the tips of CDR-like loops, c, Van der Waals’ surface of D1 with side chains of antibody epitopes coloured. Residues identified with epitopes of the Leu3a family and shown in purple (24, 25, 27, 42, 43, visible) and those identified with the L71 family are shown in yellow (88, 89, visible). The view is roughly as in b. d, Electrostatic potential surface computed with DELPHI at neutral pH, and displayed with AAK (A. Nicholls and B. Honig) at the levels of the solvent-accessible surface with a probe radius of 1.4 Å. Blue represents positive potential, red negative, and white neutral. The negative patch is associated with residues 85, 87 and 88. The view is approximately as in b. e, An all-atom representation of D1D2. Residues in the gp120-binding region from residue 41 to 59 are drawn in red. The direction of view is roughly as in Fig. 2, but the molecule has been rotated by ~90° about this view axis. This view illustrates the exposed nature of Phe 43. The actual conformation of this phenyl side chain in the crystal is at least partly determined by lattice interactions, but its highly exposed nature would also be expected to persist in other conformations accessible in solution, f, Stereoview of the molecular surface in the major gp120-binding region of D1. Atoms are drawn as in e, and are enveloped by the surface in contact with a probe sphere of 1.4 Å radius as displayed by QUANTA (Polygen). The view is taken after rotation from e by ~90° about the horizontal axis.