Structure and Recognition of a Novel HIV-1 gp120-gp41 Interface Antibody that Caused MPER Exposure through Viral Escape
Fig 5
The CAP248-2B CDR-L3 interacts with the viral membrane.
Two docking orientations for the CAP248-2B Fab are modelled with (A) the CDR-L3 in close proximity to the viral membrane, and (B) the CDR-L3 in close proximity to the fusion peptide. The trimer is coloured as in Fig 4, and the Fab heavy and light chains shown in forest and olive green respectively, and the approximate location of the viral membrane is indicated with dotted lines. In the zoomed panel insets, the CDR-H1 (pink) and CDR-L3 (yellow) are shown in their predicted binding locations for each model. The fusion peptide is colored purple and shown with surface representation. (C) Neutralization of three heterologous viruses by CAP248-2B and related CDR-H1 and CDR-L3 mutants. Percentage inhibition was plotted on the y-axis versus antibody concentration on the x-axis. Dotted lines indicate y-axis intersections for IC80, IC50, and IC20. (D) ELISA showing binding of CAP248-2B and related mutant antibodies to the BG505(gp120)-CAP45(gp41) chimeric SOSIP trimer. Absorbance readings are plotted on the y-axis and antibody concentration on the x-axis. CAP256-VRC26.09 and F105 are used are positive and negative control antibodies. (E) Anti-cardiolipin antibody ELISA, labelled as in D. (F) HEp-2 cell reactivity assays comparing a no antibody control to 50 μg/mL concentrations of either 4E10 (positive control), 35O22 (negative control), or CAP248-2B.