Fig. 4: Comparison of CD4 binding to asymmetric and pseudo-symmetric Env trimers.

a The gp120 chain of a gp120–CD4 complex (PDB 3JWO) was superposed on all three gp120 subunits of the asymmetric AE2.1 Env trimer (colored according to chains). The docked two-domain CD4 molecules are shown as magenta ribbons. Interprotomer interfaces 1 and 3 have larger opening angles; interprotomer interface 2 has a small opening angle. In interface 2, CD4 binding to the AE2.1 Env brings it into very close proximity to the glycans on Asn 301 modeled on the basis of the observed density map. b The panels in the left column show Asn 301 glycan structures from the AE2.1 model, with real cryo-EM density surrounding the yellow glycan residues. The panels in the right column show Asn 301 Man7 glycans with additional terminal mannose residues constructed in silico, colored the same as their associated Env protomers. At each interprotomer interface, any atoms on the Asn 301 glycans that are within 4 Å of CD4 are colored red. At interprotomer interface 3, the distance between the center of mass of the whole Man7 glycan and that of one β-sheet (Lys 2–Gly 6) on CD4 is 13.7 Å; the distance for the other β-sheet (Lys 166–Glu 169) on CD4 is 10.7 Å. c The gp120 chain of a gp120–CD4 complex (PDB 3JWO) was superposed on all three gp120 subunits of a C3 pseudo-symmetric AE2.1 Env trimer. This pseudo-symmetric AE2.1 Env structure is identical to the one used in Fig. 1e. CD4 is closer to the Asn 301 glycan on the adjacent protomer for the pseudo-symmetric AE2.1 trimer compared with its binding to the more open interfaces of the asymmetric AE2.1 trimer; however, no clash is encountered with the pseudo-symmetric trimer. d The left panel shows the Asn 301 glycan structure on one interprotomer interface of the C3 pseudo-symmetric AE2.1 Env trimer; the right panel shows the Asn 301 Man7 glycan with additional terminal mannose residues constructed in silico. Any atoms on the Asn 301 glycan that are within 4 Å of CD4 are colored red. The distance between the center of mass of the whole Man7 glycan and that of one β-sheet (Lys 2–Gly 6) on CD4 is 10.2 Å; the distance for the other β-sheet (Lys 166–Glu 169) on CD4 is 8.7 Å.