6N7J
BDBV223 Fab bound to synthetic peptide of Bundibugyo virus Glycoprotein Stalk
Summary for 6N7J
| Entry DOI | 10.2210/pdb6n7j/pdb |
| Descriptor | BDBV223 antibody heavy chain, BDBV223 antibody light chain, Envelope glycoprotein (3 entities in total) |
| Functional Keywords | antibody, antiviral protein, viral protein-immune system complex, viral protein/immune system |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 6 |
| Total formula weight | 100628.70 |
| Authors | King, L.B.,West, B.R.,Saphire, E.O. (deposition date: 2018-11-27, release date: 2019-03-20, Last modification date: 2024-10-16) |
| Primary citation | King, L.B.,West, B.R.,Moyer, C.L.,Gilchuk, P.,Flyak, A.,Ilinykh, P.A.,Bombardi, R.,Hui, S.,Huang, K.,Bukreyev, A.,Crowe Jr., J.E.,Saphire, E.O. Cross-reactive neutralizing human survivor monoclonal antibody BDBV223 targets the ebolavirus stalk. Nat Commun, 10:1788-1788, 2019 Cited by PubMed Abstract: Three Ebolavirus genus viruses cause lethal disease and lack targeted therapeutics: Ebola virus, Sudan virus and Bundibugyo virus. Monoclonal antibody (mAb) cocktails against the surface glycoprotein (GP) present a potential therapeutic strategy. Here we report two crystal structures of the antibody BDBV223, alone and complexed with its GP2 stalk epitope, an interesting site for therapeutic/vaccine design due to its high sequence conservation among ebolaviruses. BDBV223, identified in a human survivor of Bundibugyo virus disease, neutralizes both Bundibugyo virus and Ebola virus, but not Sudan virus. Importantly, the structure suggests that BDBV223 binding interferes with both the trimeric bundle assembly of GP and the viral membrane by stabilizing a conformation in which the monomers are separated by GP lifting or bending. Targeted mutagenesis of BDBV223 to enhance SUDV GP recognition indicates that additional determinants of antibody binding likely lie outside the visualized interactions, and perhaps involve quaternary assembly or membrane-interacting regions. PubMed: 30996276DOI: 10.1038/s41467-019-09732-7 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.684 Å) |
Structure validation
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