Structure of the Ebola Virus Glycoprotein Bound to An Antibody From a Human Survivor

Journal Article · Wed May 20 04:00:00 EDT 2009 · Nature 454:137,2008

OSTI ID:953079

Lee, J E; Fusco, M L; Hessell, A J; Oswald, W B; Burton, D R; Saphire, E O

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 unraveling the mechanism of EBOV GP-mediated fusion and for future immunotherapeutic development.

• Research Organization: Stanford Linear Accelerator Center (SLAC)
• Sponsoring Organization: USDOE
• DOE Contract Number: AC02-76SF00515
• OSTI ID: 953079
• Report Number(s): SLAC-REPRINT-2009-205
• Journal Information: Nature 454:137,2008, Journal Name: Nature 454:137,2008 Vol. 454
• Country of Publication: United States
• Language: English

Related Subjects

36 MATERIALS SCIENCE
CRYSTAL STRUCTURE
GLOBAL POSITIONING SYSTEM
GLYCOPROTEINS
MEMBRANES
Other
OTHER
PROTEINS