1.G.16.1.3
Envelope glycoprotein 160, GP160, Env protein of 854 aas.  This is the intact protein from which GP41 is derived by proteolysis. Envelope glycoprotein gp160 oligomerizes in the host endoplasmic reticulum predominantly into trimers. Gp160 transits in the host Golgi, where glycosylation is completed. The precursor is then proteolytically cleaved in the trans-Golgi and thereby activated by cellular furin or furin-like proteases to produce gp120 and gp41. Transmembrane protein gp41 is a class I viral fusion protein (Chen 2019). The protein has at least 3 conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During fusion of viral and target intracellular membranes, the coiled coil regions (heptad repeats) assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of viral and target cell membranes. Complete fusion occurs in host cell endosomes and is dynamin-dependent, however some lipid transfer might occur at the plasma membrane. The virus undergoes clathrin-dependent internalization long before endosomal fusion, thus minimizing the surface exposure of conserved viral epitopes during fusion and reducing the efficacy of inhibitors targeting these epitopes. Membranes fusion leads to delivery of the nucleocapsid into the cytoplasm (Klug et al. 2017). The C- and the N-terminal regions of the glycoprotein 41 ectodomain fuse membranes enriched and not enriched with cholesterol, respectively (Shnaper et al. 2004).