Anti-Ebola GP II (Clone: ABM4C78)

The Sudan ebola virus (SUDV) glycoprotein (GP) is an envelope glycoprotein that is present on the virion surface and is involved in receptor binding and mediating viral entry. It is composed of a trimer of heterodimers (GP1/GP2), where GP1 and GP2 remain covalently linked by a disulfide bond9, and the resulting GP1-GP2 pair trimerizes to form a ~450 kDa envelope spike on the viral surface. GP is synthesized as a single polypeptide of 676 amino acids in length that is post-translationally cleaved by furin to yield two subunits, GP1 and GP2. The GP2 subunit mediates virus-cell membrane fusion and viral entry. Structural analysis of the core domain of Ebola virus GP2 indicates that the fusion-active conformation of GP2 is similar to that of the other class I membrane fusion proteins, suggesting a common membrane fusion mechanism. In the endosome, GP2 releases from GP1 and undergoes irreversible conformational changes that drive fusion with host endosomal membranes. GP2 contains an N-terminal peptide, a hairpin-forming fusion loop, and two heptad repeats connected by a functionally important linker. The first heptad repeat of GP2 is wound around the base of GP1 in a metastable, prefusion-specific conformation. Protein function: GP1 is responsible for binding to the receptor(s) on target cells. Interacts with CD209/DC-SIGN and CLEC4M/DC-SIGNR which act as cofactors for virus entry into the host cell. Binding to CD209 and CLEC4M, which are respectively found on dendritic cells (DCs), and on endothelial cells of liver sinusoids and lymph node sinuses, facilitate infection of macrophages and endothelial cells. These interactions not only facilitate virus cell entry, but also allow capture of viral particles by DCs and subsequent transmission to susceptible cells without DCs infection (trans infection). Binding to the macrophage specific lectin CLEC10A also seem to enhance virus infectivity. Interaction with FOLR1/folate receptor alpha may be a cofactor for virus entry in some cell types, although results are contradictory. Members of the Tyro3 receptor tyrosine kinase family also seem to be cell entry factors in filovirus infection. Once attached, the virions are internalized through clathrin-dependent endocytosis and/or macropinocytosis. After internalization of the virus into the endosomes of the host cell, proteolysis of GP1 by two cysteine proteases, CTSB/cathepsin B and CTSL/cathepsin L presumably induces a conformational change of GP2, allowing its binding to the host entry receptor NPC1 and unmasking its fusion peptide to initiate membranes fusion. [The UniProt Consortium]