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

Human immunodeficiency virus type 1 glycoprotein 41 (HIV-1 gp41) is the transmembrane subunit of the viral envelope glycoprotein, essential for mediating the fusion of the viral envelope and the host cell membrane (UniProt P04578). It contains two critical alpha-helical domains known as heptad repeat 1 (HR1) and heptad repeat 2 (HR2) that collapse into a six-helix bundle (6HB) to facilitate viral entry (Chan et al., 1997). The term "clamp epitopes" refers to the use of these heptad repeat sequences in "molecular clamp" technology, an engineering platform designed to stabilize viral fusion proteins in their pre-fusion conformation (Watterson et al., 2016). While this technology was intended to improve vaccine efficacy for various viruses, the use of gp41-derived sequences as the clamping mechanism led to the elicitation of gp41-specific antibodies, which are the primary targets of fusion inhibitors like Enfuvirtide (PubChem CID 16130199). Consequently, these epitopes are significant both as targets for antiretroviral therapy and as a cautionary factor in vaccine design due to potential diagnostic interference with HIV screening (Chappell et al., 2021). Understanding the structural dynamics of these heptad repeats is vital for developing next-generation entry inhibitors and broadly neutralizing antibodies.

Other names

gp41Transmembrane glycoproteinTMEnv gp41Heptad repeat 1 (HR1)Heptad repeat 2 (HR2)HIV-1 gp41 heptad repeat–derived clamp epitopes

Fusion inhibition by binding to the HR1 or HR2 regions of gp41 to prevent the formation of the six-helix bundle (6HB) required for viral-host membrane fusion (Chan et al., 1997; PubChem CID 16130199).