CD4 binding site on envelope glycoprotein gp120 (CD4BS on gp120)

The CD4 binding site on envelope glycoprotein gp120 is a highly conserved, functionally critical region of the HIV-1 viral envelope spike protein that mediates the initial attachment of the virus to the host cell by binding to the CD4 receptor on T lymphocytes and other cells[4][5][6]. Upon engaging CD4, gp120 undergoes major conformational changes that expose or create a binding site for chemokine coreceptors CCR5 or CXCR4, facilitating viral entry by promoting membrane fusion with the host cell[1][2][4]. The CD4 binding site is a recessed pocket formed by conserved regions of the gp120 protein and includes the "Phe43 cavity," which interacts directly with phenylalanine 43 (Phe43) of the CD4 molecule[6]. This region is a target for broadly neutralizing antibodies (such as VRC01 and IgG1b12), but immune recognition is hindered by conformational flexibility, variable glycosylation, and masking of key epitopes[5][7]. The CD4 binding site is considered a prime therapeutic and vaccine target, but the intricate structural dynamics and immune evasion strategies of gp120 make it a difficult target for durable clinical interventions[2][7].

Other names

CD4 binding pocket on gp120gp120-CD4 interfaceCD4BSHIV-1 gp120 CD4 binding site

Inhibition of viral entry by blocking gp120 interaction with CD4 (antibodies, CD4 mimetics) Prevention of conformational change necessary for coreceptor binding and membrane fusion