Human immunodeficiency virus type 1 glycoprotein 41 (gp41) (gp41)

Human immunodeficiency virus type 1 glycoprotein 41 (gp41) is a transmembrane subunit of the HIV-1 envelope protein complex (Env), which is essential for viral entry into host cells [2, 10, 14]. It is initially synthesized as part of the gp160 precursor, which is cleaved by host proteases into the surface subunit gp120 and the transmembrane subunit gp41 [7, 14]. While gp120 mediates the initial attachment to CD4 and co-receptors, gp41 undergoes a dramatic conformational change to facilitate the fusion of the viral and host cell membranes [1, 10]. This process involves the insertion of a hydrophobic fusion peptide into the target cell membrane and the formation of a stable six-helix bundle from its heptad repeat regions (HR1 and HR2) [1, 8, 10]. By bringing the membranes into close proximity, gp41 enables the delivery of the viral core into the host cytoplasm, thereby establishing infection [1, 10]. In clinical practice, gp41 is the primary target for fusion inhibitors, a class of antiretroviral drugs that block the virus at the entry stage [1, 3, 13]. For example, Enfuvirtide mimics the HR2 domain and binds to the HR1 region, preventing the structural rearrangements needed for membrane fusion [1, 4, 6]. Beyond its structural role, gp41 has also been implicated in inducing apoptosis in bystander immune cells, contributing to the pathogenesis of HIV/AIDS [2].

Other names

Transmembrane glycoprotein gp41TMEnvelope glycoprotein gp41ENVgp41

Fusion inhibition via competitive binding to the heptad repeat 1 (HR1) region of gp41, which prevents the interaction between HR1 and HR2 and thereby blocks the formation of the six-helix bundle required for membrane fusion.