HIV-1 envelope glycoprotein gp120–gp41 interface

The HIV-1 envelope glycoprotein gp120–gp41 interface is the interaction region between the surface subunit gp120 and the transmembrane subunit gp41 of the HIV-1 envelope spike (Env) complex. This trimeric structure is crucial for HIV-1 cell entry, mediating viral attachment via gp120 binding to the host CD4 receptor and chemokine co-receptors, followed by gp41-driven viral–cell membrane fusion. The interface is a dynamic, structurally complex region and a critical target for broadly neutralizing antibodies and fusion inhibitors, but its high degree of conformational plasticity and glycan shielding make it challenging for vaccine and drug design. Therapies targeting this site aim to block the entry process and prevent HIV-1 infection, but viral escape remains a major challenge.

Other names

HIV-1 Env trimer interfaceHIV-1 envelope glycoprotein interfaceHIV-1 gp120–gp41 quaternary interfaceHIV-1 envelope spike interface

Inhibitor peptides (e.g., enfuvirtide) block refolding of gp41, preventing membrane fusion. Monoclonal antibodies bind to quaternary epitopes at the gp120–gp41 interface, blocking conformational changes required for fusion or neutralizing the virus. Some small molecules disrupt the conformational transitions needed for fusion (rare, mostly experimental)