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Title | Convergence of a common solution for broad ebolavirus neutralization by glycan cap-directed human antibodies. |
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Journal, issue, pages | Cell Rep, Vol. 35, Issue 2, Page 108984, Year 2021 |
Publish date | Apr 13, 2021 |
Authors | Charles D Murin / Pavlo Gilchuk / Philipp A Ilinykh / Kai Huang / Natalia Kuzmina / Xiaoli Shen / Jessica F Bruhn / Aubrey L Bryan / Edgar Davidson / Benjamin J Doranz / Lauren E Williamson / Jeffrey Copps / Tanwee Alkutkar / Andrew I Flyak / Alexander Bukreyev / James E Crowe / Andrew B Ward / |
PubMed Abstract | Antibodies that target the glycan cap epitope on the ebolavirus glycoprotein (GP) are common in the adaptive response of survivors. A subset is known to be broadly neutralizing, but the details of ...Antibodies that target the glycan cap epitope on the ebolavirus glycoprotein (GP) are common in the adaptive response of survivors. A subset is known to be broadly neutralizing, but the details of their epitopes and basis for neutralization are not well understood. Here, we present cryoelectron microscopy (cryo-EM) structures of diverse glycan cap antibodies that variably synergize with GP base-binding antibodies. These structures describe a conserved site of vulnerability that anchors the mucin-like domains (MLDs) to the glycan cap, which we call the MLD anchor and cradle. Antibodies that bind to the MLD cradle share common features, including use of IGHV1-69 and IGHJ6 germline genes, which exploit hydrophobic residues and form β-hairpin structures to mimic the MLD anchor, disrupt MLD attachment, destabilize GP quaternary structure, and block cleavage events required for receptor binding. Our results provide a molecular basis for ebolavirus neutralization by broadly reactive glycan cap antibodies. |
External links | Cell Rep / PubMed:33852862 / PubMed Central |
Methods | EM (single particle) / X-ray diffraction |
Resolution | 3.002 - 9.9 Å |
Structure data | EMDB-22839, PDB-7kej: EMDB-22841: Bundibugyo virus GP (mucin deleted) bound to antibody Fab BDBV-43 and ADI-15878 EMDB-22842, PDB-7kex: EMDB-22847, PDB-7kf9: EMDB-22848: Ebola virus GP (mucin deleted, Makona strain) bound to antibody Fab EBOV-442 and EBOV-515 EMDB-22851: Bundibugyo virus GP (mucin deleted) bound to antibody Fab BDBV-329 and EBOV-515 EMDB-22852: EMDB-22853: Ebola virus GP (mucin deleted, Makona strain) bound to antibody Fab EBOV-437 and EBOV-515 PDB-7kfg: |
Chemicals | ChemComp-NAG: ChemComp-PEG: |
Source |
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Keywords | VIRAL PROTEIN/Immune System / ebolavirus / glycan cap / antibody / broadly neutralizing / filovirus / VIRAL PROTEIN / VIRAL PROTEIN-Immune System complex / IMMUNE SYSTEM |