Neutralization of Virus Infectivity by Antibodies: Old Problems in New Perspectives
Figure 4
NAbs bind with different stoichiometries to oligomeric antigens. The images show electron-microscopy-based reconstructions of soluble trimers derived from the same Clade A isolate as in Figure 2 at 23 Å resolution. (a) The propeller-like top view and the side view of the trimer with one Fab directed to the CD4-binding site (PGV04) on each of the three gp120 subunits. (b) The same trimer is shown in complex with a soluble form of CD4 and the Fab of an antibody that binds to the coreceptor-binding site (17b). This NAb neutralizes poorly as IgG and better as a Fab, because the epitope is not constitutively present and is relatively inaccessible in the viral entry complex when induced by CD4 interactions. Three copies each of CD4 and Fab molecules can be seen in the top view. (c) The same combinations as in (a) and (b) are shown first and last in the row. The second and fourth panels represent trimers in complex with the Fabs of two NAbs (PGT122 and PGT135) that bind to different epitopes and with different angles from each other and from PGV04 and 17b. In the middle is a NAb with the unusual stoichiometry of one Fab per trimer, PG9, which binds preferentially to trimers and at an oblique angle to an epitope with direct contributions from two subunits. The blue mesh delineates the trimer itself. The figure is reproduced from Sanders et al. [103].
