Env-CD4 interaction. (A) Left, the cryo-EM (cryogenic electron microscopy) structure BG505 DS-SOSIP.664 Env trimer in complex with 4D CD4 and PGT145 Fab (pdb ID: 5U1F; [82]) is shown with gp120 in cyan, gp41 in brown, CD4 in blue and PGT145 Fab in gray. Right, the cryo-EM structure of B41 SOSIP.664 Env trimer in complex with 2D CD4 and 17b (pdb ID: 5VN3; [80]) is shown with gp120 in cyan, gp41 in brown, CD4 in blue, and 17b Fab in gray. (B) Env-CCR5 interaction. Left, overall structure of the 4D CD4-gp120-CCR5 complex (pdb ID: 6MET; [83]) shown in ribbon diagram. N, N-terminus; C, C-terminus; ECL2, extracellular loop 2. V3 loop and the bridging sheet of gp120 are also indicated. Right, close-up views of the interfaces between gp120 and CCR5. The N-terminus of CCR5 is attaching to the surface of the four-stranded bridging β sheet formed by the V1V2 stem and β21–β22 of gp120. Residues Ser7, Pro 8, sulfated Tyr 10, sulfated Tyr14, Tyr15, and Pro19, as well as the disulfide between Cys20 and Cys269 of CCR5 are highlighted in the stick model. The O-linked glycan at Ser7 is also shown. V3 is inserting into the CRS2 of CCR5. The conserved GPGR motif of V3 is highlighted in the stick model, and ECL2 of CCR5 is indicated.