Ebolavirus glycoprotein base region (GP1 base region) (GP base region or GP1 base)

The "Ebolavirus GP base region" refers to a specific subdomain within the Ebolavirus glycoprotein (GP), which is a critical envelope protein involved in virus entry into host cells. The GP is cleaved into two subunits: GP1 (responsible for cell attachment) and GP2 (mediates membrane fusion). The base region is part of GP1 and lies adjacent to GP2, forming structural and functional interfaces crucial for viral infection. The Ebolavirus glycoprotein base region is a structurally distinct portion of the surface glycoprotein GP, specifically within the GP1 subunit. It forms a semi-circular, hydrophobic interface that interacts intimately with the internal fusion loop and heptad repeat of GP2, stabilizing the prefusion conformation of the viral envelope. It contains critical cysteine residues that form disulfide bonds with GP2 and is a key structural clamp preventing premature fusion activation. The base region is a major epitope for broadly neutralizing antibodies, making it an attractive therapeutic target. Because GP is the only surface protein of Ebolavirus, its base region is central to viral attachment to host cells, membrane fusion, and entry. Targeting the base region with antibodies or inhibitors can block viral infection, and its unique features differentiate it from other viral fusion proteins, such as those found in HIV and influenza. The base region includes residues 33–69, 95–104, 158–167, and 176–189 (GP1). It is partly occluded by glycan and mucin-like domains before proteolytic cleavage in the host endosome, which is necessary for exposure of the receptor-binding site. The region's flexible and hydrophobic nature is essential for the tightly regulated fusion process and is recognized by survivorship-derived neutralizing antibodies, such as KZ52 and mAb114. Experimental disruption of key lysine residues (K95, K114, K115, K140) in the base region impairs host cell binding, demonstrating its functional significance.

Other names

GP1 base regionEbola GP baseEbolavirus GP1 baseEbola glycoprotein base

Direct inhibition (neutralization) of the GP base region blocks virus-cell interaction and membrane fusion. Steric (physical) occlusion of receptor-binding sites by targeted antibodies or molecules.