The unliganded gp120 subunit and CD4-induced changes. (A and B) Crystal structure of the outer domain of the gp120 core (17) was fitted into the cryo-EM map of the unliganded Env trimer and is shown from two perspectives parallel to the viral membrane. The approximate location of the V4 variable region, which was not resolved in the crystal structure, is indicated by a broken line. (C and D) Secondary structure organization of the inner domain of gp120 was approximated in the cryo-EM map of the unliganded Env trimer, which is viewed from two perspectives parallel to the viral membrane. (E and F) For comparison of the unliganded precursor state (E) and the CD4-bound state (F) of the gp120 core, the gp120 outer domains (blue) are aligned in the same orientation. The gp120 core in the unliganded precursor state is derived as described in A–D above, and the CD4-bound gp120 core structure is from an X-ray crystal structure (Protein Data Bank ID: 3JWD).