HIV-1 envelope glycoprotein subunit gp41 (gp41)

HIV-1 envelope glycoprotein subunit gp41 is the **transmembrane component of the HIV envelope glycoprotein complex** (Env), which also includes the surface subunit gp120. Together, gp41 and gp120 form a trimeric spike on the viral surface responsible for **virus attachment, membrane fusion, and entry into host cells**[1][6]. gp120 mediates initial binding to host CD4 and chemokine receptors (CCR5/CXCR4), triggering structural rearrangements in gp41. This causes gp41 to undergo a dramatic conformational change, exposing its fusion peptide and facilitating **fusion between the viral and host cell membranes**[1][2][5]. gp41 contains several functional regions: the **fusion peptide**, N-terminal and C-terminal heptad repeats, a loop region, the membrane-proximal external region (MPER), transmembrane domain, and cytoplasmic tail[1][5]. The characteristic **six-helix bundle formation** of gp41 is essential for the fusion process, and peptides mimicking the heptad repeats (such as enfuvirtide) can inhibit this step, making gp41 a validated target for antiviral drugs[2][3][6]. gp41 is highly conserved among HIV-1 strains, but its membrane association and structural flexibility make it a difficult target for neutralizing antibodies and small molecules. Nonetheless, **broadly neutralizing antibodies targeting the MPER region of gp41** or fusion inhibitors directed at heptad repeats remain promising approaches for therapy and vaccine development[5][6].

Other names

HIV envelope protein gp41HIV Env gp41HIV-1 gp41Viral envelope glycoprotein gp41

Fusion inhibition (drugs bind to heptad repeat regions of gp41, preventing formation of the fusion-active six-helix bundle and thus blocking membrane fusion and viral entry)