Schematic illustration of HIV gp41 and its NHR- and CHR-derived peptides. The gp41 numbering of HIV-1HXB2 is used. FP, fusion peptide; NHR, N-terminal heptad repeat; CHR, C-terminal heptad repeat; TRM, tryptophan-rich motif; TM, transmembrane domain; CT, cytoplasmic tail. The positions and sequences corresponding to the T20-resistant site and pocket-forming site in the NHR are shown in blue. The italic “abcdefg” corresponds to the positions of the amino acids per heptad repeat sequence. The positions and sequences corresponding to the M-T hook structure, pocket-binding domain, and TRM in the CHR are shown in green, red, and purple, respectively. (Chol) and (C16) represent cholesterol and palmitic acid, respectively; PEG8, 8-unit polyethylene glycol. Engineered residues in LP-50 and LP-51 are shown in pink, and the potential salt bridges are indicated by solid black lines.