6PCI
EBOV GPdMuc (Makona) in complex with rEBOV-520 and rEBOV-548 Fabs
Summary for 6PCI
| Entry DOI | 10.2210/pdb6pci/pdb |
| EMDB information | 20301 |
| Descriptor | Virion spike glycoprotein, rEBOV-548 Fab heavy chain, rEBOV-548 Fab light chain, ... (8 entities in total) |
| Functional Keywords | ebola, filovirus, antibody, synergy, immune system, viral protein |
| Biological source | Ebola virus More |
| Total number of polymer chains | 18 |
| Total formula weight | 453276.66 |
| Authors | Ward, A.B.,Murin, C.D.,Alkutkar, T. (deposition date: 2019-06-17, release date: 2020-03-11, Last modification date: 2024-10-16) |
| Primary citation | Gilchuk, P.,Murin, C.D.,Milligan, J.C.,Cross, R.W.,Mire, C.E.,Ilinykh, P.A.,Huang, K.,Kuzmina, N.,Altman, P.X.,Hui, S.,Gunn, B.M.,Bryan, A.L.,Davidson, E.,Doranz, B.J.,Turner, H.L.,Alkutkar, T.,Flinko, R.,Orlandi, C.,Carnahan, R.,Nargi, R.,Bombardi, R.G.,Vodzak, M.E.,Li, S.,Okoli, A.,Ibeawuchi, M.,Ohiaeri, B.,Lewis, G.K.,Alter, G.,Bukreyev, A.,Saphire, E.O.,Geisbert, T.W.,Ward, A.B.,Crowe Jr., J.E. Analysis of a Therapeutic Antibody Cocktail Reveals Determinants for Cooperative and Broad Ebolavirus Neutralization. Immunity, 52:388-403.e12, 2020 Cited by PubMed Abstract: Structural principles underlying the composition of protective antiviral monoclonal antibody (mAb) cocktails are poorly defined. Here, we exploited antibody cooperativity to develop a therapeutic mAb cocktail against Ebola virus. We systematically analyzed the antibody repertoire in human survivors and identified a pair of potently neutralizing mAbs that cooperatively bound to the ebolavirus glycoprotein (GP). High-resolution structures revealed that in a two-antibody cocktail, molecular mimicry was a major feature of mAb-GP interactions. Broadly neutralizing mAb rEBOV-520 targeted a conserved epitope on the GP base region. mAb rEBOV-548 bound to a glycan cap epitope, possessed neutralizing and Fc-mediated effector function activities, and potentiated neutralization by rEBOV-520. Remodeling of the glycan cap structures by the cocktail enabled enhanced GP binding and virus neutralization. The cocktail demonstrated resistance to virus escape and protected non-human primates (NHPs) against Ebola virus disease. These data illuminate structural principles of antibody cooperativity with implications for development of antiviral immunotherapeutics. PubMed: 32023489DOI: 10.1016/j.immuni.2020.01.001 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (4.12 Å) |
Structure validation
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