5OMZ
Solution structure of domain III (DIII)of Zika virus Envelope protein
Summary for 5OMZ
| Entry DOI | 10.2210/pdb5omz/pdb |
| NMR Information | BMRB: 34167 |
| Descriptor | Envelope Protein (1 entity in total) |
| Functional Keywords | zika virus envelope protein domain, viral protein, zikv |
| Biological source | Zika virus (strain Mr 766) (ZIKV) |
| Total number of polymer chains | 1 |
| Total formula weight | 12479.39 |
| Authors | Zerbe, O.,Bardelli, M. (deposition date: 2017-08-02, release date: 2017-10-04, Last modification date: 2024-06-19) |
| Primary citation | Wang, J.,Bardelli, M.,Espinosa, D.A.,Pedotti, M.,Ng, T.S.,Bianchi, S.,Simonelli, L.,Lim, E.X.Y.,Foglierini, M.,Zatta, F.,Jaconi, S.,Beltramello, M.,Cameroni, E.,Fibriansah, G.,Shi, J.,Barca, T.,Pagani, I.,Rubio, A.,Broccoli, V.,Vicenzi, E.,Graham, V.,Pullan, S.,Dowall, S.,Hewson, R.,Jurt, S.,Zerbe, O.,Stettler, K.,Lanzavecchia, A.,Sallusto, F.,Cavalli, A.,Harris, E.,Lok, S.M.,Varani, L.,Corti, D. A Human Bi-specific Antibody against Zika Virus with High Therapeutic Potential. Cell, 171:229-241.e15, 2017 Cited by PubMed Abstract: Zika virus (ZIKV), a mosquito-borne flavivirus, causes devastating congenital birth defects. We isolated a human monoclonal antibody (mAb), ZKA190, that potently cross-neutralizes multi-lineage ZIKV strains. ZKA190 is highly effective in vivo in preventing morbidity and mortality of ZIKV-infected mice. NMR and cryo-electron microscopy show its binding to an exposed epitope on DIII of the E protein. ZKA190 Fab binds all 180 E protein copies, altering the virus quaternary arrangement and surface curvature. However, ZIKV escape mutants emerged in vitro and in vivo in the presence of ZKA190, as well as of other neutralizing mAbs. To counter this problem, we developed a bispecific antibody (FIT-1) comprising ZKA190 and a second mAb specific for DII of E protein. In addition to retaining high in vitro and in vivo potencies, FIT-1 robustly prevented viral escape, warranting its development as a ZIKV immunotherapy. PubMed: 28938115DOI: 10.1016/j.cell.2017.09.002 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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