Models of Fusion based on CD4-gp120 Co-receptor Interaction

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10-17-96; 14:58 DVP- 86189424978;# 2/ 4
Points to consider for model of HIV-1 env-mediated model:
(1) CT4 molecules undergo change after binding of gp 120. Probably, a "bent" occurs in the
hinge region (between the second and third domain).
(2) The gpl20 molecules undergo conformational changes after binding to CD4. For
example, it was shown that the V3 loop is closer to the CD4-binding groove.
(3) Our model suggests that the two (or threc) CD4 molecules that interact with the gp 120-41
oligomer interact with higher avidity with the co-receptor molecules. These interactions result in
lateral mobility of these complexes allowing a reduction in the gap between the virus and target
cells and creation of an hydrophobic environment.
(4) Under the new conditions, the gp4l undergoes conformational changes resulting in
exposure of the N-terminal hydrophobic region (also known as the "fusion peptidc") that inserts
into the target membrane, destabilizes it, and leads fusion of the membranes.