Model for cooperative subunit interactions within the HIV-1 Env
oligomer. For simplicity, only two gp120/gp41 complexes are shown.
Labeling indicates gp120, gp41, CD4, and coreceptor (CoR); inactive Env
regions are designated by X. Different shapes distinguish the
preactivated and activated states of gp120; different shading
distinguishes the gp120 subunits activated directly by CD4 binding
(black) versus indirectly by subunit interactions (gray).
(A) Wild-type Env. gp120 subunits on both complexes bind
to CD4 and undergo a conformational change to expose determinants
critical for coreceptor interaction. Both gp120 subunits bind to
coreceptor, leading to activation of both gp41 subunits for fusion
peptide insertion. (B) Complementation between one Env
variant with a defective fusion peptide and another with a defective
CD4 binding site. The gp120 subunit on one complex binds to CD4 and
undergoes the conformational change exposing coreceptor interaction
determinants. The functional gp41 subunit on the other complex is
activated for fusion peptide insertion. We also presume that the
coreceptor interaction determinants are indirectly exposed on the other
gp120 subunit via concerted subunit interactions and contribute to gp41
activation (as described for D below).
(C) Complementation between one Env variant with a
defective fusion peptide and another with inactive coreceptor
interaction determinants. The gp120 subunits on both complexes bind to
CD4 and undergo the associated conformational changes. The coreceptor
interaction determinants are functional on only one gp120 subunit; this
is sufficient to activate the functional gp41 subunit on the other
complex for fusion peptide insertion. (D)
Complementation between one Env variant with a defective CD4 binding
site and another with inactive coreceptor binding determinants. The
gp120 subunit on one complex binds to CD4 and undergoes the associated
conformational change. Although the coreceptor binding determinants on
this subunit are inactive, cooperative interactions lead to a concerted
conformational change in the other gp120 subunit, which then interacts
with coreceptor and activates both gp41 subunits for fusion peptide
insertion.