Envelope glycoprotein GP120

Envelope glycoprotein GP120 (or gp120) is a glycoprotein exposed on the surface of the HIV envelope. It was discovered by Professors Tun-Hou Lee and Myron "Max" Essex of the Harvard School of Public Health in 1988. The 120 in its name comes from its molecular weight of 120 kDa. Gp120 is essential for virus entry into cells as it plays a vital role in attachment to specific cell surface receptors. These receptors are DC-SIGN, Heparan Sulfate Proteoglycan and a specific interaction with the CD4 receptor, particularly on helper T-cells. Binding to CD4 induces the start of a cascade of conformational changes in gp120 and gp41 that lead to the fusion of the viral membrane with the host cell membrane. Binding to CD4 is mainly electrostatic although there are van der Waals interactions and hydrogen bonds. Gp120 is coded by the HIV env gene, which is around 2.5 kb long and codes for around 850 amino acids. The primary env product is the protein gp160, which gets cleaved to gp120 (~480 amino acids) and gp41 (~345 amino acids) in the endoplasmatic reticulum by the cellular protease furin. The crystal structure of core gp120 shows an organization with an outer domain, an inner domain with respect to its termini and a bridging sheet. Gp120 is anchored to the viral membrane, or envelope, via non-covalent bonds with the transmembrane glycoprotein, gp41. Three gp120s and gp41s combine in a trimer of heterodimers to form the envelope spike, which mediates attachment to and entry into the host cell. Since gp120 plays a vital role in the ability of HIV-1 to enter CD4+ cells, its evolution is of particular interest. Many neutralizing antibodies bind to sites located in variable regions of gp120, so mutations in these regions will be selected for strongly. The diversity of env has been shown to increase by 1-2% per year in HIV-1 group M and the variable units are notable for rapid changes in amino acid sequence length. Increases in gp120 variability result in significantly elevated levels of viral replication, indicating an increase in viral fitness in individuals infected by diverse HIV-1 variants.