Summary for 7YAR
| Entry DOI | 10.2210/pdb7yar/pdb |
| EMDB information | 33718 |
| Descriptor | heavy chain, light chain, E protein, ... (4 entities in total) |
| Functional Keywords | virus complexed with antibody, virus |
| Biological source | Homo sapiens More |
| Total number of polymer chains | 12 |
| Total formula weight | 330327.89 |
| Authors | Shu, B.,Thiam-Seng, N.,Lok, S. (deposition date: 2022-06-28, release date: 2023-01-04, Last modification date: 2024-07-03) |
| Primary citation | Adams, C.,Carbaugh, D.L.,Shu, B.,Ng, T.S.,Castillo, I.N.,Bhowmik, R.,Segovia-Chumbez, B.,Puhl, A.C.,Graham, S.,Diehl, S.A.,Lazear, H.M.,Lok, S.M.,de Silva, A.M.,Premkumar, L. Structure and neutralization mechanism of a human antibody targeting a complex Epitope on Zika virus. Plos Pathog., 19:e1010814-e1010814, 2023 Cited by PubMed Abstract: We currently have an incomplete understanding of why only a fraction of human antibodies that bind to flaviviruses block infection of cells. Here we define the footprint of a strongly neutralizing human monoclonal antibody (mAb G9E) with Zika virus (ZIKV) by both X-ray crystallography and cryo-electron microscopy. Flavivirus envelope (E) glycoproteins are present as homodimers on the virion surface, and G9E bound to a quaternary structure epitope spanning both E protomers forming a homodimer. As G9E mainly neutralized ZIKV by blocking a step after viral attachment to cells, we tested if the neutralization mechanism of G9E was dependent on the mAb cross-linking E molecules and blocking low-pH triggered conformational changes required for viral membrane fusion. We introduced targeted mutations to the G9E paratope to create recombinant antibodies that bound to the ZIKV envelope without cross-linking E protomers. The G9E paratope mutants that bound to a restricted epitope on one protomer poorly neutralized ZIKV compared to the wild-type mAb, demonstrating that the neutralization mechanism depended on the ability of G9E to cross-link E proteins. In cell-free low pH triggered viral fusion assay, both wild-type G9E, and epitope restricted paratope mutant G9E bound to ZIKV but only the wild-type G9E blocked fusion. We propose that, beyond antibody binding strength, the ability of human antibodies to cross-link E-proteins is a critical determinant of flavivirus neutralization potency. PubMed: 36626401DOI: 10.1371/journal.ppat.1010814 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (5.9 Å) |
Structure validation
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