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.
Lee
Jeffrey E
JE
Department of Immunology and Microbial Science, The Scripps Research Institute, 10550 North Torrey Pines Road, Mail Drop IMM-2, La Jolla, California 92037, USA.
Fusco
Marnie L
ML
Hessell
Ann J
AJ
Oswald
Wendelien B
WB
Burton
Dennis R
DR
Saphire
Erica Ollmann
EO
D000818:Animals; D000914:Antibodies, Viral / Q000235:genetics / Q000276:immunology*; D001666:Binding Sites, Antibody; D002403:Cathepsins / Q000378:metabolism; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D018360:Crystallography, X-Ray; D015023:Democratic Republic of the Congo; D029043:Ebolavirus / Q000737:chemistry* / Q000276:immunology; D006023:Glycoproteins / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D008561:Membrane Fusion; D008958:Models, Molecular; D011487:Protein Conformation; D011991:Receptors, Virus / Q000737:chemistry / Q000378:metabolism; D017741:Survivors
D000914:Antibodies, Viral; D006023:Glycoproteins; D011991:Receptors, Virus; D002403:Cathepsins