Structure of the Ebola virus glycoprotein bound to a human survivor antibody
By Jeffrey E. Lee, M. Fusco, A. Hessell, W. B. Oswald, D. Burton, E. Saphire. Nature, 2008
703 citations recorded by the source corpus.
Ebola virus (EBOV) entry requires the surface glycoprotein (GP) to initiate attachment and fusion of viral and host membranes. Here we report the crystal structure of EBOV GP in its trimeric, pre-fusion conformation (GP1+GP2) bound to a neutralizing antibody, KZ52, derived from a human survivor of the 1995 Kikwit outbreak. Three GP1 viral attachment subunits assemble to form a chalice, cradled by the GP2 fusion subunits, while a novel glycan cap and projected mucin-like domain restrict access to the conserved receptor-binding site sequestered in the chalice bowl. The glycocalyx surrounding GP is likely central to immune evasion and may explain why survivors have insignificant neutralizing antibody titres. KZ52 recognizes a protein epitope at the chalice base where it clamps several regions of the pre-fusion GP2 to the amino terminus of GP1. This structure provides a template for unravelling the mechanism of EBOV GP-mediated fusion and for future immunotherapeutic development.
Subfields: Epidemiology, Infectious Diseases
View Paper: https://www.semanticscholar.org/paper/5f5392e387b0ba57ab029789b613893ff36b6e12
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Citations in the corpus
- Viral membrane fusion (2015, background): “Although the initial cleavage occurs in the producing cell, generating a trimer of disulfide-linked GP(1):GP(2) subunits[46], fusion activation requires cathepsin-mediated cleavage after uptake into the new host cell, stripping GP(1) of much of its mass[47], and subsequent interaction with a specifi”
- Viral membrane fusion (2008, positive): “Although the initial cleavage occurs in the producing cell, generating a trimer of disulfide-linked GP(1):GP(2) subunits (Lee et al., 2008), fusion activation requires cathepsin-mediated cleavage after uptake into the new host cell, stripping GP(1) of much of its mass (Chandran et al.”
- Naïve Human Antibody Libraries for Infectious Diseases (2018, background): “Neutralizing antibodies target the base of GP while the non-neutralizing antibodies will bind to the glycan cap and mucin-like domains which functions as an external domain for the viral attachment and fusion [188] [189] [190] [191] [192] .”
- Crystal structure of a soluble cleaved HIV-1 envelope trimer (2013, background): “Overall, the central trimeric coiled-coil arrangement of the fusion protein (gp41) surrounded by three receptor subunits (gp120) is a characteristic of type-1 membrane-fusion proteins (47-49).”