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

The Human immunodeficiency virus type 1 glycoprotein 41 heptad repeat 1 (HIV-1 gp41 HR1) domain is a vital structural element of the gp41 transmembrane subunit, which facilitates the fusion of viral and host cell membranes. During the infection process, the HR1 domain transitions into a triple-stranded coiled-coil that acts as a central core for the viral fusion machinery (UniProt P04578). The subsequent binding of the heptad repeat 2 (HR2) domain into the hydrophobic grooves of this HR1 core forms a six-helix bundle (6HB), a process that provides the energy necessary to bring the viral and cellular membranes together for fusion (Chan et al., 1997). As a therapeutic target, the HR1 domain is the site of action for fusion inhibitors such as Enfuvirtide, which mimics the HR2 region to competitively bind the HR1 grooves and block 6HB formation (Greenberg et al., 2004). This inhibition prevents the virus from entering host CD4+ T-cells, thereby reducing viral replication. Despite its efficacy, the HR1 domain is prone to mutations that confer drug resistance, necessitating its use as part of combination antiretroviral therapy (DrugBank DB00109). Clinical monitoring of patients targeting this domain typically involves measuring viral load and CD4+ counts to assess treatment success.

Other names

HR1 domainN-terminal heptad repeatNHRN-HRgp41 HR1

Fusion inhibition by binding to the HR1 hydrophobic grooves, preventing the formation of the six-helix bundle (6HB) required for viral-cell membrane fusion.