Broadly resistant HIV-1 against CD4-binding site neutralizing antibodies
Fig 5
Structural basis of the signature resistance mutations.
(A) Major epitope regions of CD4-binding site antibodies on the HIV-1 Env in its pre-fusion closed conformation. The inner domain contact, Loop D, CD4-binding loop, Loop V5 and the outer domain exiting loop are colored cyan, orange, yellow, magenta and marine blue respectively. (B) Overlay of the boundaries of epitopes for VH1-2-derived VRC01-class antibodies (green line) and VRC13 (blue line) onto the different structural regions. (C) Resistance conferred by mutations that disrupt salt bridges and hydrogen bonds between gp120 and CD4bs antibodies. HIV-1 gp120 residues were colored and labeled according to their structural regions and the antibody residues were labeled by source and location, such as Asp100 of antibody N6. (D) Resistance conferred by mutations providing steric hinderance on loop D and the outer domain exiting loop. Potential clashes between resistance mutations and the antibodies were marked as red discs. The heavy chains of VRC01 class antibodies were colored in shades of green and CDR H3 of VRC13 was colored red. Light chains were colored slate. (E) Resistance conferred by mutations providing steric hinderance on β23. (F) Resistance conferred by mutations providing steric hinderance through bulkier residues or a glycan on loop V5.