Human immunodeficiency virus type 1 glycoprotein 41 (gp41)

Human immunodeficiency virus type 1 glycoprotein 41 (gp41) is a critical transmembrane subunit of the HIV-1 envelope protein (Env) that mediates the fusion between the viral envelope and the host cell membrane (UniProt: P04578). Following the binding of the surface subunit gp120 to the CD4 receptor and a co-receptor (CCR5 or CXCR4), gp41 undergoes a dramatic conformational rearrangement (PMID: 22403442). This process involves the insertion of its hydrophobic fusion peptide into the host cell membrane and the subsequent folding of its heptad repeat regions (HR1 and HR2) into a stable six-helix bundle (6HB), which pulls the viral and cellular membranes together for fusion (Chan et al., Cell, 1997). As a vital component of the viral entry machinery, gp41 is a major therapeutic target for fusion inhibitors. Drugs like Enfuvirtide bind to the HR1 region, preventing the formation of the 6HB and effectively blocking viral entry into the host cell (FDA: Fuzeon Label). Monitoring for resistance mutations in the gp41 gene is essential for maintaining therapeutic efficacy in patients (PMID: 15530379).

Other names

Transmembrane glycoprotein gp41TM subunitEnv gp41HIV-1 gp41 fusion protein

Fusion inhibition by binding to the N-terminal heptad repeat (NHR/HR1) region of gp41, thereby preventing the formation of the six-helix bundle (6HB) required for viral-host membrane fusion (PMID: 12734000).