Figure 1.
Structure-based approach focuses on recognition hotspots for VRC01-class antibodies. (a) Heavy-chain Gly54 to Trp mutation to mimic Phe43CD4 occupying a hydrophobic pocket on gp120. (b) Swap of VRC01 CDR H3 with VRC07 CDR H3 to increase binding surface between gp120 and the CDR H3. (c) Deletion of three residues of N-terminal light chain to better accommodate various lengths and conformations of the V5 region of gp120. (d) Replacement of framework region 3 with VRC03 framework region 3 (03FR3) to extend its interaction to the neighboring protomer. The structure of core gp120 in complex with VRC07-G54W (PDB ID: 4OLZ) is shown, superimposed on the structure of BG505 DS-SOSIP in complex with VRC01 Fab (PDB ID: 6NNF)