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Structure paper

TitleStructural Basis of Pan-Ebolavirus Neutralization by an Antibody Targeting the Glycoprotein Fusion Loop.
Journal, issue, pagesCell Rep, Vol. 24, Issue 10, Page 2723-22732.e4, Year 2018
Publish dateSep 4, 2018
AuthorsCharles D Murin / Jessica F Bruhn / Zachary A Bornholdt / Jeffrey Copps / Robyn Stanfield / Andrew B Ward /
PubMed AbstractMonoclonal antibodies (mAbs) with pan-ebolavirus cross-reactivity are highly desirable, but development of such mAbs is limited by a lack of a molecular understanding of cross-reactive epitopes. The ...Monoclonal antibodies (mAbs) with pan-ebolavirus cross-reactivity are highly desirable, but development of such mAbs is limited by a lack of a molecular understanding of cross-reactive epitopes. The antibody ADI-15878 was previously identified from a human survivor of Ebola virus Makona variant (EBOV/Mak) infection. This mAb demonstrated potent neutralizing activity against all known ebolaviruses and provided protection in rodent and ferret models against three ebolavirus species. Here, we describe the unliganded crystal structure of ADI-15878 as well as the cryo-EM structures of ADI-15878 in complex with the EBOV/Mak and Bundibugyo virus (BDBV) glycoproteins (GPs). ADI-15878 binds through an induced-fit mechanism by targeting highly conserved residues in the internal fusion loop (IFL), bridging across GP protomers via the heptad repeat 1 (HR1) region. Our structures provide a more complete description of the ebolavirus immunogenic landscape, as well as a molecular basis for how rare but potent antibodies target conserved filoviral fusion machinery.
External linksCell Rep / PubMed:30184505 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution2.1 - 4.29 Å
Structure data

8935

6dzl

EMDB-8935, PDB-6dzl:
Ebola virus Makona variant GP (mucin-deleted) in complex with pan-ebolavirus human antibody ADI-15878 Fab
Method: EM (single particle) / Resolution: 4.14 Å

8936

6dzm

EMDB-8936, PDB-6dzm:
Bundibugyo virus GP (mucin-deleted) in complex with pan-ebolavirus human antibody ADI-15878 Fab
Method: EM (single particle) / Resolution: 4.29 Å

PDB-6dzn:
Pan-ebolavirus human antibody ADI-15878 Fab
Method: X-RAY DIFFRACTION / Resolution: 2.1 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

ChemComp-CL:
Unknown entry / Chloride

ChemComp-AE3:
2-(2-ETHOXYETHOXY)ETHANOL / 2-(2-Ethoxyethoxy)ethanol

ChemComp-PG4:
TETRAETHYLENE GLYCOL / precipitant*YM / Polyethylene glycol

ChemComp-HOH:
WATER / Water

Source
  • Ebola virus
  • Homo sa (virus)
  • zaire ebolavirus
  • homo sapiens (human)
  • Bundibugyo virus
  • bundibugyo ebolavirus
KeywordsVIRAL PROTEIN / Ebola / antibody / pan-ebolavirus / internal fusion loop / HR1 / glycoprotein / IMMUNE SYSTEM / ADI-15878 / immunotherapeutic / Ebola virus / Bundibugyo virus

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