Structural highlights
FunctionPublication Abstract from PubMedAntibodies 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 beta-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. Convergence of a common solution for broad ebolavirus neutralization by glycan cap-directed human antibodies.,Murin CD, Gilchuk P, Ilinykh PA, Huang K, Kuzmina N, Shen X, Bruhn JF, Bryan AL, Davidson E, Doranz BJ, Williamson LE, Copps J, Alkutkar T, Flyak AI, Bukreyev A, Crowe JE Jr, Ward AB Cell Rep. 2021 Apr 13;35(2):108984. doi: 10.1016/j.celrep.2021.108984. PMID:33852862[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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