Human immunodeficiency virus type 1 glycoprotein 41 heptad repeat 1 (HIV-1 gp41 HR1)

Human immunodeficiency virus type 1 glycoprotein 41 (gp41) is the transmembrane subunit of the viral envelope protein (Env) that mediates the fusion of viral and host cell membranes (UniProt P04578). During the entry process, following gp120 binding to CD4 and coreceptors, gp41 transitions into a transient 'pre-hairpin' intermediate state where the N-terminal heptad repeat 1 (HR1) region is exposed as a triple-stranded alpha-helical coiled-coil (PMID: 9144287). This HR1 coiled-coil serves as a critical scaffold for the C-terminal heptad repeat 2 (HR2) to fold back upon, forming a stable six-helix bundle (6HB) that drives membrane apposition and fusion. Therapeutic agents known as fusion inhibitors target the hydrophobic grooves of the HR1 trimer in this pre-hairpin state, physically preventing the formation of the 6HB (PMID: 11486082). By blocking this conformational change, the drugs prevent the viral genome from entering the host cell, making it a vital target for treating multi-drug resistant HIV-1 infections.

Other names

gp41 N-terminal heptad repeatNHRHeptad repeat 1gp41 HR1 domainHIV-1 gp41 N-terminal coiled-coil

Fusion inhibition by binding to the HR1 coiled-coil to prevent the formation of the six-helix bundle (6HB) fusion intermediate (PMID: 11486082).