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

The Human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein gp41 heptad repeat 1 (HR1) trimer is a transient structural intermediate essential for viral entry into host cells [1, 12]. Following the binding of the gp120 subunit to cellular receptors, gp41 undergoes a conformational transition into a 'prehairpin' state, where three HR1 regions assemble into a central, triple-stranded coiled-coil trimer [2, 18]. This trimeric core provides conserved hydrophobic grooves that serve as the target site for the C-terminal heptad repeat (HR2) regions to fold back and form a stable six-helix bundle (6HB) [4, 15]. The formation of this bundle drives the fusion of viral and host membranes, allowing the viral genome to enter the cytoplasm [3, 15]. Because the HR1 trimer is exposed only during this intermediate step, it represents a vulnerable target for fusion inhibitors [9, 11]. Therapeutic agents, such as the approved drug Enfuvirtide, bind to these HR1 grooves to competitively block 6HB formation [2, 20]. This interaction effectively prevents the virus from completing the fusion process and infecting the target cell [9, 11]. Research into this target has also led to the development of next-generation peptides and antibodies with broader neutralizing activity [6, 20].

Other names

NHR trimer [11]N-terminal heptad repeat trimer [1]gp41 HR1 coiled-coil trimer [2]Prehairpin intermediate core [12, 18]

Fusion inhibition by binding to the HR1 trimer grooves and preventing the formation of the six-helix bundle (6HB) required for membrane fusion [2, 4, 11].