Fig. 3.

In contrast to VRC01, A12 or b12 cannot be accommodated on native trimeric Env without steric clash. (A) Top view of a hypothetical, glycosylated model for A12-bound Env if no conformational changes occurred in the trimer upon A12 binding. Three copies of the complex of A12 with monomeric gp120 (PDB ID code 3RJQ) were aligned to the trimeric molecular model for gp120 in the unliganded state (PDB ID code 3DNN). (B and C) Top views of a model for glycosylated trimeric gp120 in the unliganded state, as in A, but with either b12 (B) or VRC01 (C) Fab bound. The models show that steric clashes would occur if A12 or b12 were to bind the native state without conformational rearrangements. Coordinates show gp120 (red), VHH A12 (cyan, PDB ID: 3RJQ), b12 Fab (blue, PDB ID: 2NY7), and VRC01 Fab (gold, PDB ID: 3NGB).