HIV-1 transmembrane glycoprotein gp41 (gp41)

The HIV-1 transmembrane glycoprotein gp41 is a critical component of the viral envelope complex, working in tandem with the surface glycoprotein gp120 to facilitate viral entry into host cells (UniProt: P04578). Upon gp120 binding to CD4 and co-receptors, gp41 undergoes a major conformational reorganization where its hydrophobic fusion peptide inserts into the host cell membrane. This is followed by the interaction of its heptad repeat 1 (HR1) and heptad repeat 2 (HR2) domains to form a stable six-helix bundle, which draws the viral and host membranes together for fusion (PubMed: 22837340). Because this step is essential for the HIV life cycle, gp41 serves as a validated therapeutic target for fusion inhibitors (NIH: PMC4274534). Enfuvirtide, the first-in-class fusion inhibitor, specifically binds the HR1 region to block this fusion process. However, the clinical utility of gp41-targeting drugs is often challenged by the necessity for parenteral administration and the potential for rapid emergence of resistance through mutations within the HR1 domain (StatPearls: NBK535359, PubMed: 15306941).

Other names

Envelope glycoprotein gp41Transmembrane proteingp41 subunitTM proteinEnvelope surface glycoprotein gp41

Inhibition of HIV-1 entry by binding to the heptad repeat 1 (HR1) region of the gp41 subunit, which prevents the conformational change required for the formation of the six-helix bundle and subsequent viral-cell membrane fusion.