Figure 1.

Gp41 and HIV‐1 fusion. (a) Schematic representation of the HIV‐1 gp41 sequence with regions labeled as follows: FP, fusion peptide (magenta); NHR, N‐terminal heptad repeat (orange); CHR, C‐terminal heptad repeat (blue); MPER, membrane proximal external region; TM, transmembrane anchor; CP, cytoplasmic domain. The residue numbers, defining the boundaries of the regions, correspond to positions in gp160 of HIV‐1_HXB2. (b) The fusion of viral and host membranes mediated by gp41. The viral (brown) and host membranes (cyan) are shown at the top and bottom, respectively. (1) The binding of gp120 (red) to CD4 (green) and co‐receptor CXCR4 or CCR5 (purple) triggers a conformational change that releases gp120 from gp41 (yellow), which enables the insertion of the gp41 fusion peptides (magenta) into the host cell membrane, resulting in the exposure of the helical NHR (orange) pre‐hairpin intermediate. (2) The CHR helices (blue) zip up along the outside of the NHR coiled‐coil, which leads to the formation of 6HB and pulls the viral and host membranes together. (3) This results in the formation of a fusion pore, which completes the membrane fusion process. T20 competes with CHR for binding to NHR and thus prevents the conformational changes required for 6HB formation and membrane fusion.