@article{ad6f3ffa1f404fd692e0ce94c69105fc,
title = "Structure of the Ebola virus glycoprotein bound to an antibody from a human survivor",
abstract = "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.",
author = "Lee, {Jeffrey E.} and Fusco, {Marnie L.} and Hessell, {Ann J.} and Oswald, {Wendelien B.} and Burton, {Dennis R.} and Saphire, {Erica Ollmann}",
note = "Funding Information: Acknowledgements We thank C. Kimberlin (The Scripps Research Institute), the staff at the Advanced Light Source beamlines 8.3.1, 5.0.2, 4.2.2, 8.2.2 and 12.3.1 and the Stanford Synchrotron Radiation Laboratory beamlines 11-1 and 9-2 for data collection support, and D. Abelson and members of the Ollmann Saphire Laboratory for assistance, comments and suggestions. The Advanced Light Source and Stanford Synchrotron Radiation Laboratory are national user facilities operated on behalf of the US Department of Energy. We also thank A. Olson and J. Huntoon for generation of tangible molecular models for analysis of receptor-binding surfaces. E.O.S. and D.R.B. are funded by the US National Institutes of Health, and E.O.S. and J.E.L. are supported by a Career Award from the Burroughs Wellcome Fund and a fellowship from the Canadian Institutes of Health Research, respectively. This is manuscript no. 19375 from The Scripps Research Institute.",
year = "2008",
month = jul,
day = "10",
doi = "10.1038/nature07082",
language = "English (US)",
volume = "454",
pages = "177--182",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7201",
}