Structure and Recognition of a Novel HIV-1 gp120-gp41 Interface Antibody that Caused MPER Exposure through Viral Escape
Fig 7
The CAP248-2B epitope is proximal to Env glycans, but not affected by glycan heterogeneity.
Schematic of CAP248-2B bound trimer (colored as in Fig 4 with gp120 shown in transparent surface grey scale) including modelled (NAG)2MAN3 basic glycans at epitope proximal N88, N611, N616, N625, and N637 residues (colored brown, yellow, pink, purple, and blue respectively). Two views are shown: (A) Top view, and (B) Side view zoom. Relocation of the N88 glycan between 35O22 and CAP248-2B bound states is indicated. (C) Wong glycan array data for CAP248-2B. Weak binding was detected for two hybrid glycans, but significant binding of >500 a.u. was only detected for one biantennary mono-sialylated complex N-glycan (indicated by the glycan schema). (D) Neutralization of CAP45 by CAP248-2B when compared to epitope proximal glycan mutants. The S613A mutant that removed the glycan at N611 but maintains the amino acid side chain properties is shown with red dashed lines and open circles. Percentage inhibition was plotted on the y-axis versus CAP248-2B antibody concentration on the x-axis. (E) Neutralization of the CAP45 N611D single mutant, and various N611D including double glycan mutants, plotted as in D. (F) Neutralization of heterologous tier-2 strains CAP45, CNE52, CAP228, and ZM249 when grown normally (black lines), with co-transfected furin (dashed pink lines), or in the presence of kifunensine (blue lines), swainsonine (cyan lines), and an O-linked glycosylation inhibitor (dashed orange lines), or in a GnTI deficient cell line (grey lines). Neutralization was also assessed in the presence of sCD4 at predetermined IC40 concentrations for each virus (dashed green lines), or after a 24 hour virus-target cell incubation period (red lines). Graphs are plotted as in D.