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

Article

关键词: GP120 ENVELOPE GLYCOPROTEIN;    NEUTRALIZING HUMAN-ANTIBODY;    INTERNAL FUSION PEPTIDE;    HEMORRHAGIC-FEVER;    MARBURG VIRUSES;    VIRION GLYCOPROTEINS;    CYSTEINES FLANKING;    NONHUMAN-PRIMATES;    VACCINE PROTECTS;    FILOVIRUS ENTRY;   

DOI  :  10.1038/nature07082

来源: SCIE

【 摘 要 】

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.

【 授权许可】

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