Figure 4. Structures of gp41 trimers visualized by X-ray crystallography and of gp41 helices within soluble gp140 trimers visualized by cryo-electron microscopy.

(A, B) Superposition of 24 structures reported for trimeric variants of gp41 N-terminal and C-terminal helices in the canonical post-fusion “six-helix bundle” conformation, shown as top (A) and front (B) views. All gp41 coordinates were aligned to the 1AIK structure [44]. The PDB IDs of entries included in the superposition are 1AIK, 2X7R, 2XRA, 3MAC, 3MA9, 2CMR, 3VIE, 1F23, 3AHA, 2Z2T, 3P30, 1ENV, 1K34, 1DLB, 1SZT, 1DF4, 3CP1, 3CYO, 2OT5, 1QR9, 1I5X, 1I5Y, 3VTP, and 3K9A. (C, D) Top and front views of the structure, determined by cryo-electron microscopy, at ~ 9 Å resolution, of trimeric gp140 in an activated, but pre-fusion conformation [36]. The structure represents a complex between the entire ectodomain of trimeric Env and Fab fragments of the monoclonal antibody 17b. The three central densities are assigned to the three copies of the N-heptad repeat helix in gp41, which form a three-helix motif that is more open than that observed in the post-fusion structures shown in panels (A) and (B). The density map is shown fitted with coordinates for the gp120 core (red), heavy (green) and light (yellow) chains of the Fv fragment of the 17b antibody, and the gp41 N-terminal helices (cyan). The gp120 and 17b coordinates are from PDB structure 1GC1 [9], while the gp41 coordinates are from PDB structure 1AIK [44].