Fig. 3. Structure of an engineered CRF01_AE SOSIP.664 Env trimer in complex with temsavir.

a Overall structures of trimers complexed with chaperone Fabs of 10–1074 and 8ANC195 antibodies shown as cartoon with LMHS mutations highlighted in red within one gp120 promoter. Envelope sugars are shown as gray sticks. b Changes to overall trimer assembly, calculated as changes in position of gp120 relative to gp41 (referred to as trimer ‘opening’) of CRF01_AE_ T/F100 SOSIP.664 variants as compared to BG505 SOSIP.664 (PDB ID: 4ZMJ⁷⁷). The relative position for each gp120 in the trimer is calculated based on the α-carbon position for residue 375 at the base of the CD4 Phe43 binding pocket (shown as colored spheres for each structure) relative to the gp41 trimer center (gray sphere, Centr, calculated for all trimers aligned based on the α-carbon positions of the central gp41 α7 helices). The distances between Centr and the ³⁷⁵Cα of each protomer (a–c) and the ³⁷⁵Cα atoms of neighboring protomers (d–f) are shown to indicate the extent of the protomer rearrangement relative to gp41. The clockwise rotations of the gp120 subunits are calculated as angles relative to apo BG505 SOSIP (shown and labeled a-a’, b-b’, and c-c’). The BG505 SOSIP.664 bound to CD4 (PDB: 5THR⁷⁸) is shown as a reference to the ‘open’ CD4-triggered conformation of trimer. c Table summarizing a–f distances and a-a’, b-b’ and c-c’ rotation angles for CRF01_AE_ T/F100 SOSIP.664 complex variants relative to the unbound BG505 SOSIP trimer (PDB: 4ZMJ⁷⁷).