HIV-1 envelope glycoprotein gp120, CD4 binding site (gp120 CD4BS)

The CD4 binding site is a recessed, conformationally dynamic pocket on the HIV-1 gp120 envelope glycoprotein that interacts directly with the extracellular domain of the CD4 receptor on host T cells[4][5]. Binding to CD4 triggers extensive conformational rearrangements in gp120, exposing additional epitopes and the chemokine coreceptor binding site (mainly for CCR5 or CXCR4), which are required for viral fusion and entry[4][2]. The structural plasticity and glycosylation of gp120 contribute to immune evasion, presenting challenges for vaccine and drug design[6][5][2]. Despite these barriers, the CD4 binding site is considered a primary target for neutralizing antibodies, entry inhibitors, and vaccine immunogen development, and its structure-function relationships continue to inform HIV therapeutic research[3][2][1].

Other names

CD4BSHIV gp120 CD4-binding domaingp120-CD4 siteHIV-1 Env CD4 binding siteCD4 attachment site on EnvCD4 receptor interface (rare)

Blockade of gp120-CD4 interaction, preventing viral attachment/entry; Induction of neutralizing conformational changes or destabilization of Env; Inhibition of downstream coreceptor binding (CCR5/CXCR4)