6PLK
Crystal structure of ZIKV-116 Fab in complex with ZIKV envelope DIII
Summary for 6PLK
| Entry DOI | 10.2210/pdb6plk/pdb |
| Descriptor | ZIKV-116 heavy chain, ZIKV-116 light chain, Env, ... (4 entities in total) |
| Functional Keywords | human antibody, zikv-diii, antiviral protein, structural genomics, center for structural genomics of infectious diseases, csgid |
| Biological source | Homo sapiens More |
| Total number of polymer chains | 6 |
| Total formula weight | 118949.84 |
| Authors | Zhao, H.,Fremont, D.H.,Center for Structural Genomics of Infectious Diseases (CSGID) (deposition date: 2019-07-01, release date: 2019-11-20, Last modification date: 2024-11-13) |
| Primary citation | Zhao, H.,Xu, L.,Bombardi, R.,Nargi, R.,Deng, Z.,Errico, J.M.,Nelson, C.A.,Dowd, K.A.,Pierson, T.C.,Crowe, J.E.,Diamond, M.S.,Fremont, D.H. Mechanism of differential Zika and dengue virus neutralization by a public antibody lineage targeting the DIII lateral ridge. J.Exp.Med., 217:-, 2020 Cited by PubMed Abstract: We previously generated a panel of human monoclonal antibodies (mAbs) against Zika virus (ZIKV) and identified one, ZIKV-116, that shares germline usage with mAbs identified in multiple donors. Here we show that ZIKV-116 interferes with ZIKV infection at a post-cellular attachment step by blocking viral fusion with host membranes. ZIKV-116 recognizes the lateral ridge of envelope protein domain III, with one critical residue varying between the Asian and African strains responsible for differential binding affinity and neutralization potency (E393D). ZIKV-116 also binds to and cross-neutralizes some dengue virus serotype 1 (DENV1) strains, with genotype-dependent inhibition explained by variation in a domain II residue (R204K) that potentially modulates exposure of the distally located, partially cryptic epitope. The V-J reverted germline configuration of ZIKV-116 preferentially binds to and neutralizes an Asian ZIKV strain, suggesting that this epitope may optimally induce related B cell clonotypes. Overall, these studies provide a structural and molecular mechanism for a cross-reactive mAb that uniquely neutralizes ZIKV and DENV1. PubMed: 31757867DOI: 10.1084/jem.20191792 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.3 Å) |
Structure validation
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