Figure 1.
Three-Dimensional Reconstruction of SIV Virions from Cryo-Electron Tomography
(A) A slice through the xy plane of a reconstructed tomogram from the −6-μm defocus dataset. The spike complexes are clearly visible on the viral surface. Some of the cores appear disrupted, reflecting AT-2 treatment. Scale bar represents 100 nm.
(B) Surface rendering of one of the virions. The membrane is represented in blue, the core in red and the spikes in orange.
(C) The same virus as in (B) viewed after removing half of the viral envelope along the dotted line to reveal the core. The density between the core and the membrane has not been rendered.
Figure 2.
Reconstruction of the Env Spike, Filtered to 28 Å, and Rendered
(A) A rendered view of the complex at a 2 sigma contour level. The chirality of the distal portion is evident.
(B) As in (A), rotated 60° around the 3-fold symmetry axis.
(C) A slab through the density in the orientation represented in panel (B), revealing the cavity at the centre of the structure. The membrane is coloured in cyan. The volume corresponding to gp41 has been coloured in gray, and the remaining gp120 volume in orange.
Scale bar = 100 Å.
Figure 3.
Fitting of the Molecular Model of Unliganded SIV gp120 into the Reconstruction
(A) and (B) Views of the first fitting (shown from above in panel [A] and from the side in panel [B]). The variable loops V1V2 (black), V4, and V5 (light blue) are positioned on the surface of the trimer, whereas V3 (red) is closer to the trimer interface. The receptor binding pocket (magenta) is exposed, although partially protected by sugars (blue) and variable loops. The bridging sheet (green) is hidden at the trimer–gp41 interface. Sugar residues are exposed on the surface.
(C) and (D) Views of the second fitting (shown from above in panel [C] and from the side in panel [D]). The colour code is the same as in panels (A) and (B). Variable loops V1V2, V3, V4, and V5 are exposed on the surface of the trimer. The receptor binding pocket is also exposed and partially protected by sugars. The bridging sheet is exposed, and the V3 loop could protect it from antibody binding. Sugar residues are exposed.
Figure 4.
Model for HIV/SIV Receptor Engagement, Based on the First Proposed Fitting
(A) The Env complex before CD4 binding. The bridging sheet is not accessible to co-receptor and antibodies, and the V3 loop is at the trimer interface.
(B) CD4 binding causes a conformational change and an overall rotation of the gp120 molecule. The V3 loop binds selectively to co-receptor, and the bridging sheet becomes exposed and available for co-receptor binding.