HIV-1 envelope glycoprotein gp41 N-terminal heptad repeat pocket (gp41 NHR pocket)

The HIV-1 envelope glycoprotein gp41 N-terminal heptad repeat (NHR) deep pocket is a highly conserved hydrophobic cavity essential for the viral entry process (Chan et al., 1997; PMID: 9160751). During HIV-1 infection, the gp41 subunit mediates the fusion between the viral envelope and the host cell plasma membrane. This process involves a dramatic conformational change where three NHR helices form a trimeric coiled-coil, creating three longitudinal grooves that each contain a deep pocket (Liu et al., 2002; PMID: 11752710). The C-terminal heptad repeat (CHR) region of gp41 then folds back into these grooves, with its pocket-binding domain (PBD) inserting into the NHR deep pocket to form a stable six-helix bundle (6-HB). This 6-HB formation brings the viral and cellular membranes into close proximity, facilitating fusion. Because the NHR deep pocket is critical for 6-HB stability and is highly conserved across diverse HIV-1 strains, it serves as a primary target for fusion inhibitors (He et al., 2008; PMID: 18234671). Therapeutic agents, including second-generation peptides like Albuvirtide and various small-molecule inhibitors, are designed to occupy this pocket, thereby preventing the NHR-CHR interaction and blocking viral entry (Zhang et al., 2016; PMID: 27010161).

Other names

gp41 deep pocketgp41 hydrophobic pocketNHR deep pocketgp41 fusion pocketNHR-CHR interface pocket

Inhibition of six-helix bundle (6-HB) formation by competitively binding to the NHR deep pocket, preventing the interaction between the NHR and CHR regions of gp41.