CD4 Binding Site on HIV Envelope Glycoprotein gp120 (CD4 Binding Site on gp120)

The CD4 binding site is a critical region on the HIV-1 envelope glycoprotein gp120, which mediates the initial attachment of the virus to host cells. This interaction is essential for viral entry and infection, as it triggers conformational changes in gp120 that allow subsequent binding to a chemokine coreceptor (typically CCR5 or CXCR4), ultimately leading to membrane fusion and viral entry into the host cell. The gp120 protein consists of an inner domain, an outer domain, and a bridging sheet. These domains are structurally distinct but interact closely at the CD4 binding interface. Upon engagement with CD4, significant conformational rearrangements occur within gp120. The structure around the CD4 binding site is highly conserved but shielded by variable loops (V1/V2) and extensive glycosylation, making it difficult for neutralizing antibodies to access this region effectively. This contributes significantly to immune evasion by HIV. Gp120 is encoded by the env gene (~2.5 kb), which produces a precursor protein (gp160). Gp160 is cleaved into surface-exposed gp120 (~480 amino acids) and transmembrane anchor protein gp41 (~345 amino acids).

Other names

gp120 CD4 binding siteHIV gp120 CD4 binding domainCD4bs on gp120

Attachment inhibitor; prevents HIV gp120 from binding to CD4 receptor on host cells.