Fig. 3

Structural modelling of the impact of escape mutations around the p24-Gag B81:01-TL9 epitope. a Overall structure of p24-Gag protein residues 133–283 demonstrating the position of the B*81:01-TL9 epitope (red cartoon) and the polymorphisms between the NL4-3 and SK-254 viruses (blue cartoon). The environment that is likely to be affected by mutations around the B*81:01-TL9 epitope, in helix 3, is highlighted in the black box. b Binding network (green and red sticks) around residue 188L (yellow sticks) in the NL4-3 virus, likely to be important for maintaining the protein fold between helix 3 and 4. c Modelling of the rare L188F mutation, shown to reduce viral replication capacity. This mutation could abrogate interactions between residue 188 with 184L, 198 M, 201L and 266I, possibly destabilizing the helix 3–helix 4 interface. d Binding network (green and red sticks) around residue 186T (yellow sticks) in the NL4-3 virus, likely to be important for maintaining the protein fold between helix 1 and 3. e Modelling of the T186S mutation (black arrow), shown to be detrimental to viral health. This mutation abrogates interactions between residue 186 with 152L and 147I/T (black circle), possibly destabilizing the helix 1–helix 3 interface. f Structural modeling of the T190I mutation (black arrow) that can rescue the T186S mutation, restoring viral replication capacity. Modelling suggests that new interactions can form between residue 190I and 152L (black circle), potentially restoring helix 1–helix 3 interface stability