6FLB
3H5 Fab bound to EDIII of DenV 2 Xtal form 2
Summary for 6FLB
| Entry DOI | 10.2210/pdb6flb/pdb |
| Descriptor | Domain III of Dengue virus 2, Heavy chain of 3H5 Fab, Light chain of 3H5 Fab, ... (7 entities in total) |
| Functional Keywords | dengue virus, antibody, macromolecular complex, viral protein |
| Biological source | Dengue virus 2 (DENV-2) More |
| Total number of polymer chains | 3 |
| Total formula weight | 60039.38 |
| Authors | Flanagan, A.,Renner, M.,Grimes, J.M. (deposition date: 2018-01-25, release date: 2018-10-24, Last modification date: 2024-11-13) |
| Primary citation | Renner, M.,Flanagan, A.,Dejnirattisai, W.,Puttikhunt, C.,Kasinrerk, W.,Supasa, P.,Wongwiwat, W.,Chawansuntati, K.,Duangchinda, T.,Cowper, A.,Midgley, C.M.,Malasit, P.,Huiskonen, J.T.,Mongkolsapaya, J.,Screaton, G.R.,Grimes, J.M. Characterization of a potent and highly unusual minimally enhancing antibody directed against dengue virus. Nat. Immunol., 19:1248-1256, 2018 Cited by PubMed Abstract: Dengue virus is a major pathogen, and severe infections can lead to life-threatening dengue hemorrhagic fever. Dengue virus exists as four serotypes, and dengue hemorrhagic fever is often associated with secondary heterologous infections. Antibody-dependent enhancement (ADE) may drive higher viral loads in these secondary infections and is purported to result from antibodies that recognize dengue virus but fail to fully neutralize it. Here we characterize two antibodies, 2C8 and 3H5, that bind to the envelope protein. Antibody 3H5 is highly unusual as it not only is potently neutralizing but also promotes little if any ADE, whereas antibody 2C8 has strong capacity to promote ADE. We show that 3H5 shows resilient binding in endosomal pH conditions and neutralizes at low occupancy. Immunocomplexes of 3H5 and dengue virus do not efficiently interact with Fcγ receptors, which we propose is due to the binding mode of 3H5 and constitutes the primary mechanism of how ADE is avoided. PubMed: 30323338DOI: 10.1038/s41590-018-0227-7 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.2 Å) |
Structure validation
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