Structure based prediction of the basis of enhanced LT5.J4b Env sensitivity to IgG1b12 (anti-CD4bs) and 3074 (anti-V3) MAbs.

<p>A. Amino acid residues in C2V3 region of the LT5.J4b Env that modulated neutralization sensitivity. The model was prepared in UCSF Chimera in the background of JRFL crystal structure (RSCB PDB: 2B4C). The C2V3 amino acid residues that differed between sensitive (LT5.J4b) and other resistant Envs are highlighted. Residues in dark blue are in loop D that contacts CD4 which is in close proximity to major CD4 binding residues (SSGGDPE) (shown in yellow). B Predicated conformations of LT5.J4b and LT5.J12 Env structures in the background of JRFL gp120 crystal structure (2B4C) after energy minimization. C. Spatial orientation of loop D of LT5.J4b and LT5.J12 due to mutations in C2V3 region that showed closer proximity to IgG1b12 heavy chain. D. The interaction of heavy chain of 3074 (green) with V3 loops (LT5.J4b purple, LT5.J12 yellow.