Envelope glycoprotein gp120 of HIV-1 (gp120)

Envelope glycoprotein gp120 is a ~120 kDa, surface-exposed HIV-1 protein that is central to viral entry. It binds with high specificity to the CD4 receptor, primarily on T-helper lymphocytes, triggering conformational changes that allow subsequent binding to a coreceptor (CCR5 or CXCR4) and ultimately exposing gp41 for membrane fusion. gp120 is heavily glycosylated, displays multiple variable loops (V1-V5), and is part of the Env trimeric spike complex alongside gp41 on the viral membrane. Its extreme sequence variability, glycan shield, and conformational flexibility permit immune evasion and present a major challenge for the development of neutralizing antibodies and vaccines. As such, gp120 is the principal molecular target for HIV attachment inhibitors, entry inhibitors, and many vaccine approaches.

Other names

gp120HIV-1 Env SU (surface unit of envelope glycoprotein)HIV-1 external glycoproteinHIV-1 surface glycoproteinHIV-1 envelope protein gp120HIV-1 Env

Inhibition of gp120 binding to CD4 receptor blocks HIV entry into host cells (by ibalizumab, fostemsavir). Neutralization/blocking of coreceptor binding (VRC01, b12, X5, and other antibodies). Some antibodies target specific conformational states, preventing required structural changes for fusion.