HIV-1 envelope glycoprotein gp120 C4 region (gp120 C4)

The HIV-1 envelope glycoprotein gp120 C4 region is a highly conserved segment of the surface subunit (gp120) of the HIV-1 envelope (Env) protein. It is essential for viral entry into host cells, as it participates in the formation of the CD4 binding site and the bridging sheet, which interacts with chemokine coreceptors like CCR5 or CXCR4. Binding of gp120 to the CD4 receptor induces conformational changes in the C4 region and other domains, transitioning the Env trimer from a closed to an open state and exposing the coreceptor binding site. This region is a critical target for antiretroviral drugs, most notably the attachment inhibitor fostemsavir (and its active form temsavir), which binds to gp120 to prevent its interaction with CD4. Mutations within the C4 region, such as M426L and M434I, are significant because they can confer resistance to these inhibitors. Additionally, the C4 region is a target for various neutralizing antibodies, although the virus often shields this area through conformational masking and glycosylation to evade the immune system.

Other names

Fourth conserved region of gp120gp120 C4 domainC4 region of HIV-1 gp120HIV-1 gp120 C4

Attachment inhibition and conformational stabilization