Viral envelope glycoprotein gp41 (gp41)

Viral envelope glycoprotein gp41 is a transmembrane subunit of the envelope spike complex of human immunodeficiency virus type 1 (HIV-1) and related lentiviruses[1][8]. It forms a non-covalently associated complex with gp120 on the viral surface, referred to as the envelope spike complex, which is essential for viral entry into host cells[1][3][5]. Upon gp120 binding to CD4 and a co-receptor (CCR5 or CXCR4) on the host cell, gp41 undergoes major conformational changes, exposing its fusion peptide and enabling fusion of viral and host cellular membranes[1][3][5][7]. The core of gp41 forms a stable six-helix bundle critical for the fusion process[3][4][5][6]. This process releases energy that brings the viral and cellular membranes together, allowing viral entry into the cell[5][7]. gp41 is a prime therapeutic target—most notably, the fusion inhibitor enfuvirtide disrupts this process by binding to specific heptad repeat regions, preventing the necessary conformational rearrangements for fusion[1][3][5]. gp41's membrane-proximal external region (MPER) is also recognized by broadly neutralizing antibodies and is a target for HIV vaccine development[5][7][9].

Other names

HIV envelope protein gp41HIV-1 gp41envelope glycoprotein 41Env-gp41

Inhibition of viral membrane fusion via blockade of gp41 conformational changes (e.g., enfuvirtide binds to gp41 heptad repeats, preventing the formation of the six-helix bundle required for membrane fusion)