Human immunodeficiency virus 1 envelope glycoprotein gp120 C5 region (gp120 C5)

The HIV-1 gp120 C5 region is the C-terminal domain of the surface glycoprotein gp120, which plays a critical role in the non-covalent association with the transmembrane glycoprotein gp41 (RCSB PDB 1MEQ; Guilhaudis et al., 2002). This region, along with the N-terminal C1 region, forms a key part of the gp120/gp41 protein-protein interface within the functional envelope (Env) trimer. The stability of this interface is essential for maintaining the virus in its pre-fusion state and for the subsequent conformational transitions triggered by CD4 and co-receptor binding that lead to viral-host membrane fusion (NIH, 2021). Because of its conserved nature and functional importance, the C5 region and the broader gp120/gp41 interface have emerged as significant targets for broadly neutralizing antibodies (bNAbs) such as 35O22 and VRC44 (Huang et al., 2014; Cale et al., 2024). These agents work by stabilizing the Env trimer and sterically hindering the structural rearrangements necessary for infection. Therapeutic challenges include the potential for viral escape through mutations at the interface and the risk of autoimmune responses due to molecular mimicry between the C5 region and human leukocyte antigen (HLA) class I molecules (Eur J Immunol, 1993).

Other names

C5 domain of gp120gp120 C-terminal regiongp120/gp41 interfaceC5 region of HIV-1 gp120gp120-gp41 quaternary interface

Inhibition of HIV-1 entry by binding to the gp120/gp41 interface, stabilizing the pre-fusion envelope trimer and preventing the conformational changes required for membrane fusion.