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TitleStructural and molecular basis for Ebola virus neutralization by protective human antibodies.
Journal, issue, pagesScience, Vol. 351, Issue 6279, Page 1343-1346, Year 2016
Publish dateMar 18, 2016
AuthorsJohn Misasi / Morgan S A Gilman / Masaru Kanekiyo / Miao Gui / Alberto Cagigi / Sabue Mulangu / Davide Corti / Julie E Ledgerwood / Antonio Lanzavecchia / James Cunningham / Jean Jacques Muyembe-Tamfun / Ulrich Baxa / Barney S Graham / Ye Xiang / Nancy J Sullivan / Jason S McLellan /
PubMed AbstractEbola virus causes hemorrhagic fever with a high case fatality rate for which there is no approved therapy. Two human monoclonal antibodies, mAb100 and mAb114, in combination, protect nonhuman ...Ebola virus causes hemorrhagic fever with a high case fatality rate for which there is no approved therapy. Two human monoclonal antibodies, mAb100 and mAb114, in combination, protect nonhuman primates against all signs of Ebola virus disease, including viremia. Here, we demonstrate that mAb100 recognizes the base of the Ebola virus glycoprotein (GP) trimer, occludes access to the cathepsin-cleavage loop, and prevents the proteolytic cleavage of GP that is required for virus entry. We show that mAb114 interacts with the glycan cap and inner chalice of GP, remains associated after proteolytic removal of the glycan cap, and inhibits binding of cleaved GP to its receptor. These results define the basis of neutralization for two protective antibodies and may facilitate development of therapies and vaccines.
External linksScience / PubMed:26917592 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution1.973 - 7.2 Å
Structure data

EMDB-3310:
Cryo-EM structure of Ebola GP-Fab100-Fab114 ternary complex at pH 7.4
Method: EM (single particle) / Resolution: 7.2 Å

EMDB-3311:
Cryo-EM structure of Ebola GP-Fab100-Fab114 ternary complex at pH 5
Method: EM (single particle) / Resolution: 6.7 Å

PDB-5fha:
Crystal Structure of Protective Ebola Virus Antibody 114
Method: X-RAY DIFFRACTION / Resolution: 1.973 Å

PDB-5fhb:
Crystal Structure of Protective Ebola Virus Antibody 100
Method: X-RAY DIFFRACTION / Resolution: 1.973 Å

PDB-5fhc:
Crystal Structure of Protective Human Antibodies 100 and 114 in Complex with Ebola Virus Fusion Glycoprotein (GP)
Method: X-RAY DIFFRACTION / Resolution: 6.704 Å

Chemicals

ChemComp-HOH:
WATER

ChemComp-EDO:
1,2-ETHANEDIOL

ChemComp-ACT:
ACETATE ION

Source
  • zaire ebolavirus
  • homo sapiens (human)
  • zaire ebolavirus (strain mayinga-76)
KeywordsIMMUNE SYSTEM / Ig domain / Fab / VIRAL PROTEIN/IMMUNE SYSTEM / fusion / ebola virus / glycoprotein / GP / VIRAL PROTEIN-IMMUNE SYSTEM complex

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