Structure of the Ebola virus glycoprotein bound to an antibody from a human survivor

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.