Human immunodeficiency virus type 1 envelope glycoprotein gp41 N-terminal heptad repeat region (NHR)

The Human immunodeficiency virus type 1 (HIV-1) gp41 N-terminal heptad repeat (NHR) region is a highly conserved domain within the transmembrane subunit of the viral envelope glycoprotein (UniProt: P04578). It plays a fundamental role in the viral entry process by forming a central, trimeric coiled-coil that serves as a scaffold during membrane fusion (PMID: 15134471). Following the binding of gp120 to host receptors, gp41 undergoes a dramatic conformational change where the NHR region interacts with the C-terminal heptad repeat (CHR) region to form a stable six-helix bundle (6HB) (PMID: 28834155). This 6HB formation pulls the viral and host cell membranes together, enabling the fusion of the lipid bilayers and the subsequent release of the viral capsid into the cytoplasm. As a critical intermediate in the fusion pathway, the NHR region is the primary pharmacological target for fusion inhibitors like Enfuvirtide (FDA Label: Enfuvirtide). These therapeutic agents are typically synthetic peptides that mimic the CHR region, competitively binding to the NHR grooves to block the formation of the 6HB and effectively preventing HIV-1 infection of target cells.

Other names

N-heptad repeatHR1Heptad repeat 1gp41 NHRgp41 HR1

Fusion inhibition by binding to the N-terminal heptad repeat (NHR) coiled-coil to prevent the formation of the six-helix bundle (6HB) with the C-terminal heptad repeat (CHR) (PMID: 15134471, 28834155).