Fig. 7.

Model of HIV-1 Env conformational regulation. a Changes in the β20–β21 conformation upon CD4 binding. Left, surface representation showing the location of the β20–β21 element in one gp120 subunit on the HIV-1 Env structure; the ribbon structure of β20–β21 is depicted to the right of the Env surface. Both representations are derived from the crystal structure of the HIV-1_BG505 sgp140 SOSIP.664 glycoprotein (PDB ID 4TVP)³⁰. Right, surface representation from the cryo-EM structure of HIV-1_BG505 sgp140 SOSIP.664 bound to sCD4 (PDB 5THR; the V1/V2 region is shown schematically as a yellow sphere). The β20–β21 elements from four crystal structures of gp120 from different HIV-1 clades bound to sCD4 or the DMJ-II-121 CD4-mimetic compound (PDB IDs 4I53, 4I54, 1GC1, and 1RZK) are aligned. A possible trajectory between the upstream state and the CD4-bound state was generated with the program Chimera⁵⁰. b Effects of CD4 binding on Env conformation. CD4 contacts the gp120 β20–β21 element, altering the conformation of the β20–β21 base. Both CD4 binding and changes in restraining residues allow Env to make the transition from State 1 to downstream conformations. Examples are shown of changes in restraining gp120 residues that affect particular Env transitions