Figure 4.

IP6 binding site in the mature retroviral CA lattice. (A) Composite isosurface representation of the mature CA lattice forming a conical core. Adapted from [37]. Grey: CA hexamers, red: CA pentamers. (B,C) Top and side view of the IP6 binding site in the mature CA hexamer, respectively. Left: schematic model of mature HIV-1 CA hexamer; cyan: CA_NTD, orange: CA_CTD, and red: IP6. Middle: X-ray crystallographic model of IP6 binding to mature HIV-1 CA hexamer (6BHS, top view). IP6 has been reported to bind at different heights of the HIV-1 CA_NTD pore, based on different crystal structures, shown in (C) (pdb: 6BHT (top and bottom), 6BHS (middle)). Right: model of IP6 binding in the RSV CANC hexamer, derived from a structure solved by cryo-ET and subtomogram averaging (pdb: 7NO2). Note the orientation of the IP6 molecule with four axial phosphates pointing up or down, and one axial and the equatorial phosphate pointing horizontally. The color coding for CA_NTD is as in the left panel. The IP6 molecule is shown in sphere representation in green, orange, and red. The arginines and lysines coordinating the IP6 molecule are shown in a green stick representation and are annotated. (D) Helix 1 orientation with respect to IP6 binding. Left: cylinder model of the central pore formed by helix 1. Middle and right: cross-section through helix 1 cylinders at the height of IP6 binding plane for the C6 symmetric HIV-1 CA hexamer (as seen in the middle panel of B) and the C2 symmetric RSV CA hexamer (as seen in the right panel of B), respectively. IP6 is shown as a stick model. Dashed lines show distances between the opposite Cα atoms of R18 of HIV-1 CA in the middle image and K17 of RSV CA in the right image, and emphasize the deviation of the RSV hexamer from sixfold symmetry.