Key Part of Hiv Envelope Glycoprotein Visualized

The long-sought structure of V3, a key region of HIV's gp120 envelope glycoprotein, has been determined (Science 2005, 310, 1025). V3 plays important roles in the mechanism by which HIV fuses with host cell membranes and in antibody recognition of gp120. A group led by Richard Wyatt and Peter D. Kwong of the National Institute of Allergy & Infectious Diseases obtained the structure by analyzing a complex (shown) of gp120 (gray) with HIV host-cell receptor CD4 (yellow) and an antibody (blue). The structure shows that the 35-amino acid V3 region (red) protrudes at an angle when gp120 interacts with the surface of a host cell. This finding suggests that V3 may use a molecular hooking action to select one of two host cell coreceptors required in membrane fusion. V3's “out-there” conformation also explains why many gp120-specific antibodies are elicited against the V3 loop.