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Figure 4.
Figure 4: Structural definition of a conformationally invariant,
antibody-accessible portion of the CD4-binding site. The b12-
and CD4-bound conformations of gp120 are shown in ribbon
representation, after superposition of outer domains (red). A
semitransparent molecular surface shows the contact surfaces of
b12 (green) and CD4 (yellow). Subsets of these surfaces,
corresponding to regions of conformational flexibility (for
example, of the inner domain (grey) or bridging sheet (blue)),
are delineated, as are regions of b12 contact outside of the
conserved CD4-binding site. As can be seen, functional analysis
serves to transcend the particulars of b12 binding, whereas
antibody defines accessibility. Although we have formally shown
only the b12 contact surface to be accessible in the context of
a functional viral spike, the highly effective neutralization of
D1D2-Ig  tp
and the kinetics of its association with both core and OD1
variants of gp120 suggest that the CD4-binding surface on the
outer domain is accessible.
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