Figure 4.

Molecular mimicry of gp120 binding to CD4 relative to MHC class II. (A) The CD4 D1D2–gp120 complex (ref. 42, with Fab not included for clarity) is shown in similar orientation to the complex of CD4 D1D2/I-A^k in Fig. 1. The interactions that are in common are displayed in the box, which shows the Phe-43 inserted in a hydrophobic pocket involving gp120 β15 and β23, the formation of an antiparallel mini-β-sheet between the C" strand of CD4 and β15 from gp120 as well as interactions between CD4 Arg-59 and the loop connecting β20 to β21 in gp120. Besides these core interactions, gp120 has additional contacts through the V1/V2 loop connecting the β2 and β3 strands, the ℒD loop, and the V5 loop. (B) Overlay of CD4–CA/I-A^k and CD4–gp120 (42) complexes based on hCD4 D1 (blue and pink, respectively) with I-A^k in yellow and gp120 in red. Phe-43 and Arg-59 side chains are shown.