FIG. 7.
Model of gp41ECTO and its transitions during fusion. (Left panel) Hypothetical, native prefusion configuration of gp41 (39). (Middle panel) Prehairpin intermediate form. (Right panel) Postfusion state. In the prefusion configuration, the N-terminal helix is not present, and the region around positions 559 to 569 is not helical. The I559P and related substitutions are proposed to disrupt either the formation of the N-terminal helix in the prehairpin intermediate form or the formation of the six-helix bundle. As a result, modified SOS gp140 is maintained in the prefusion configuration. The position of the T605C substitution that creates SOS gp140 is also specified, as is the adjacent intermolecular disulfide bond (yellow bar). The positions of N-linked glycans are represented as black branching structures. Only two helices from one gp41 molecule are shown, for clarity. The letters A, B, and C are added to assist with orientation of the helices.