8EF2
Crystal structure of a NHP anti-ZIKV neutralizing antibody rhMZ107-B
Summary for 8EF2
Entry DOI | 10.2210/pdb8ef2/pdb |
Descriptor | rhMZ107-B antibody heavy chain, rhMZ107-B antibody light chain, PHOSPHATE ION, ... (4 entities in total) |
Functional Keywords | zikv, zikv-specific, cross-protomer epitopes, viral protein, immune system |
Biological source | Macaca mulatta (Rhesus monkey) More |
Total number of polymer chains | 2 |
Total formula weight | 47893.03 |
Authors | Sankhala, R.S.,Joyce, M.G. (deposition date: 2022-09-07, release date: 2023-08-30, Last modification date: 2024-10-09) |
Primary citation | Sankhala, R.S.,Dussupt, V.,Donofrio, G.,Gromowski, G.D.,De La Barrera, R.A.,Larocca, R.A.,Mendez-Rivera, L.,Lee, A.,Choe, M.,Zaky, W.,Mantus, G.,Jensen, J.L.,Chen, W.H.,Gohain, N.,Bai, H.,McCracken, M.K.,Mason, R.D.,Leggat, D.,Slike, B.M.,Tran, U.,Jian, N.,Abbink, P.,Peterson, R.,Mendes, E.A.,Freitas de Oliveira Franca, R.,Calvet, G.A.,Bispo de Filippis, A.M.,McDermott, A.,Roederer, M.,Hernandez, M.,Albertus, A.,Davidson, E.,Doranz, B.J.,Rolland, M.,Robb, M.L.,Lynch, R.M.,Barouch, D.H.,Jarman, R.G.,Thomas, S.J.,Modjarrad, K.,Michael, N.L.,Krebs, S.J.,Joyce, M.G. Zika-specific neutralizing antibodies targeting inter-dimer envelope epitopes. Cell Rep, 42:112942-112942, 2023 Cited by PubMed Abstract: Zika virus (ZIKV) is an emerging pathogen that causes devastating congenital defects. The overlapping epidemiology and immunologic cross-reactivity between ZIKV and dengue virus (DENV) pose complex challenges to vaccine design, given the potential for antibody-dependent enhancement of disease. Therefore, classification of ZIKV-specific antibody targets is of notable value. From a ZIKV-infected rhesus macaque, we identify ZIKV-reactive B cells and isolate potent neutralizing monoclonal antibodies (mAbs) with no cross-reactivity to DENV. We group these mAbs into four distinct antigenic groups targeting ZIKV-specific cross-protomer epitopes on the envelope glycoprotein. Co-crystal structures of representative mAbs in complex with ZIKV envelope glycoprotein reveal envelope-dimer epitope and unique dimer-dimer epitope targeting. All four specificities are serologically identified in convalescent humans following ZIKV infection, and representative mAbs from all four groups protect against ZIKV replication in mice. These results provide key insights into ZIKV-specific antigenicity and have implications for ZIKV vaccine, diagnostic, and therapeutic development. PubMed: 37561630DOI: 10.1016/j.celrep.2023.112942 PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (2.102 Å) |
Structure validation
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