Human immunodeficiency virus type 1 envelope glycoprotein gp41 heptad repeat 1 domain (gp41 HR1) (gp41 HR1)

The Human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein gp41 heptad repeat 1 (HR1) domain is a critical structural component of the gp41 transmembrane subunit, which mediates the fusion of the viral envelope with the host cell membrane [PubMed, PMC]. Following the binding of the gp120 subunit to the CD4 receptor and a coreceptor (CCR5 or CXCR4), gp41 undergoes a dramatic conformational change that exposes the HR1 domain [PubMed, Wikipedia]. The HR1 domain then forms a central triple-stranded coiled-coil, which serves as a scaffold for the HR2 domain to bind and form a stable six-helix bundle (6HB) [PMC, Wikipedia]. This structural transition brings the viral and cellular membranes into close proximity, facilitating their fusion and the subsequent entry of the viral capsid into the host cytoplasm [PMC]. In the context of disease, the HR1 domain is essential for the infectivity of HIV-1, the causative agent of Acquired Immunodeficiency Syndrome (AIDS) [PMC, Wikipedia]. Because of its indispensable role in the viral life cycle, the HR1 domain is a primary therapeutic target for fusion inhibitors [PubMed]. Drugs such as Enfuvirtide (T-20) and Albuvirtide are synthetic peptides that competitively bind to the HR1 grooves, preventing the formation of the six-helix bundle and effectively blocking viral entry [PubMed, PMC]. However, the clinical utility of these drugs can be limited by the emergence of resistance mutations within the HR1 domain and the requirement for parenteral administration [PMC].

Other names

NHRN-terminal heptad repeatgp41 HR1 regiongp41 N-terminal coiled-coil

Fusion inhibition by binding to the HR1 domain and preventing the formation of the six-helix bundle required for viral-cell membrane fusion.