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Title | Structural Basis of Pan-Ebolavirus Neutralization by an Antibody Targeting the Glycoprotein Fusion Loop. |
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Journal, issue, pages | Cell Rep, Vol. 24, Issue 10, Page 2723-22732.e4, Year 2018 |
Publish date | Sep 4, 2018 |
Authors | Charles D Murin / Jessica F Bruhn / Zachary A Bornholdt / Jeffrey Copps / Robyn Stanfield / Andrew B Ward / |
PubMed Abstract | 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 ...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 links | Cell Rep / PubMed:30184505 / PubMed Central |
Methods | EM (single particle) / X-ray diffraction |
Resolution | 2.1 - 4.29 Å |
Structure data | EMDB-8935, PDB-6dzl: EMDB-8936, PDB-6dzm: PDB-6dzn: |
Chemicals | ChemComp-NAG: ChemComp-CL: ChemComp-AE3: ChemComp-PG4: ChemComp-HOH: |
Source |
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Keywords | VIRAL PROTEIN / Ebola / antibody / pan-ebolavirus / internal fusion loop / HR1 / glycoprotein / IMMUNE SYSTEM / ADI-15878 / immunotherapeutic / Ebola virus / Bundibugyo virus |