Pathways & interactions
Flavivirus glycoprotein, central and dimerisation domain superfamily (IPR036253)
Short name: Glycoprot_cen/dimer_sf
- Alphavirus E1 glycoprotein (IPR002548)
- Flavivirus glycoprotein central and dimerisation domain (IPR011998)
- Flaviviral glycoprotein E, central domain, subdomain 1 (IPR013755)
- Flaviviral glycoprotein E, central domain, subdomain 2 (IPR013756)
- Flaviviral glycoprotein E, dimerisation domain (IPR038055)
Flaviviruses are small, enveloped RNA viruses that use arthropods such as mosquitoes for transmission to their vertebrate hosts, and include Yellow fever virus (YFV), West Nile virus (WNV), Tick-borne encephalitis virus, Japanese encephalitis virus (JE) and Dengue virus 2 viruses [PMID: 15378043]. Flaviviruses consist of three structural proteins: the core nucleocapsid protein C (IPR001122), and the envelope glycoproteins M (IPR000069) and E. Glycoprotein E is a class II viral fusion protein that mediates both receptor binding and fusion. Class II viral fusion proteins are found in flaviviruses and alphaviruses, and are structurally distinct from class I fusion proteins from influenza virus and HIV.
Glycoprotein E is comprised of three domains: domain I (dimerisation domain) is an 8-stranded beta barrel, domain II (central domain) is an elongated domain composed of twelve beta strands and two alpha helices, and domain III (immunoglobulin-like domain) is an IgC-like module with ten beta strands. Domains I and II are intertwined [PMID: 7753193]. This superfamily represents the intertwined central and dimerisation domains.
The glycoprotein E dimers on the viral surface re-cluster irreversibly into fusion-competent trimers upon exposure to low pH, as found in the acidic environment of the endosome. The formation of trimers results in a conformational change in the hinge region of domain II, a key structural element that opens a ligand-binding hydrophobic pocket at the interface between domains I and II. The conformational change results in the exposure of a fusion peptide loop at the tip of domain II, which is required in the fusion step to drive the cellular and viral membranes together by inserting into the membrane [PMID: 12759475].
- SSF56983 (SSF56983)