7KEX

Ebola virus GP (mucin deleted, Makona strain) bound to antibody Fab EBOV-293

Summary for 7KEX

• Entry DOI: 10.2210/pdb7kex/pdb
• EMDB information: 22842
• Descriptor: Antibody Fab EBOV-293 light chain, Antibody Fab EBOV-293 heavy chain, Virion spike glycoprotein 1, ... (7 entities in total)
• Functional Keywords: ebolavirus, glycan cap, antibody, broadly neutralizing, filovirus, viral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 12
• Total formula weight: 330394.24

Authors

Murin, C.D.,Ward, A.B. (deposition date: 2020-10-13, release date: 2021-04-28)

Primary citation

Murin, C.D.,Gilchuk, P.,Ilinykh, P.A.,Huang, K.,Kuzmina, N.,Shen, X.,Bruhn, J.F.,Bryan, A.L.,Davidson, E.,Doranz, B.J.,Williamson, L.E.,Copps, J.,Alkutkar, T.,Flyak, A.I.,Bukreyev, A.,Crowe Jr., J.E.,Ward, A.B.
Convergence of a common solution for broad ebolavirus neutralization by glycan cap-directed human antibodies.
Cell Rep, 35:108984-108984, 2021

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 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.

PubMed: 33852862
DOI: 10.1016/j.celrep.2021.108984

Experimental method

ELECTRON MICROSCOPY (4.25 Å)