5N0A
Crystal structure of A259C covalently linked dengue 2 virus envelope glycoprotein dimer in complex with the Fab fragment of the broadly neutralizing human antibody EDE2 A11
Summary for 5N0A
| Entry DOI | 10.2210/pdb5n0a/pdb |
| Descriptor | Envelope Glycoprotein E, BROADLY NEUTRALIZING HUMAN ANTIBODY EDE2 A11 HEAVY CHAIN, BROADLY NEUTRALIZING HUMAN ANTIBODY EDE2 A11, ... (4 entities in total) |
| Functional Keywords | immune system-viral protein complex, dengue virus, envelope fusion protein, broadly neutralizing antibody, immune system/viral protein |
| Biological source | Dengue virus 2 More |
| Total number of polymer chains | 6 |
| Total formula weight | 203994.64 |
| Authors | Vaney, M.C.,Rouvinski, A.,Guardado-Calvo, P.,Sharma, A.,Rey, F.A. (deposition date: 2017-02-02, release date: 2017-06-07, Last modification date: 2024-11-06) |
| Primary citation | Rouvinski, A.,Dejnirattisai, W.,Guardado-Calvo, P.,Vaney, M.C.,Sharma, A.,Duquerroy, S.,Supasa, P.,Wongwiwat, W.,Haouz, A.,Barba-Spaeth, G.,Mongkolsapaya, J.,Rey, F.A.,Screaton, G.R. Covalently linked dengue virus envelope glycoprotein dimers reduce exposure of the immunodominant fusion loop epitope. Nat Commun, 8:15411-15411, 2017 Cited by PubMed Abstract: A problem in the search for an efficient vaccine against dengue virus is the immunodominance of the fusion loop epitope (FLE), a segment of the envelope protein E that is buried at the interface of the E dimers coating mature viral particles. Anti-FLE antibodies are broadly cross-reactive but poorly neutralizing, displaying a strong infection enhancing potential. FLE exposure takes place via dynamic 'breathing' of E dimers at the virion surface. In contrast, antibodies targeting the E dimer epitope (EDE), readily exposed at the E dimer interface over the region of the conserved fusion loop, are very potent and broadly neutralizing. We here engineer E dimers locked by inter-subunit disulfide bonds, and show by X-ray crystallography and by binding to a panel of human antibodies that these engineered dimers do not expose the FLE, while retaining the EDE exposure. These locked dimers are strong immunogen candidates for a next-generation vaccine. PubMed: 28534525DOI: 10.1038/ncomms15411 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.9 Å) |
Structure validation
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