smFRET imaging revealed three conformational states of Env protomers
(State 1, State 2, and State 3). State 1 Env is likely to represent a
non-liganded conformation in pre-triggered trimers that have a closed structure.
State 2 represents an intermediate conformation, which is observed for the
non-CD4-bound Env protomer in an asymmetric Env trimer where other protomer(s)
is bound to CD4. State 3 Env is observed with the Env protomer bound to CD4,
which has an open conformation. In non-liganded Env, the V1/V2 loop masks the V3
loop that binds to coreceptors, CCR5 and CXCR4. Once CD4 binds to Env, the V3
loop is exposed. High-resolution structure of State 1 Env has not been
determined. Created with BioRender.com.