5K6B
Crystal structure of prefusion-stabilized RSV F single-chain 9 DS-Cav1 variant.
Summary for 5K6B
| Entry DOI | 10.2210/pdb5k6b/pdb |
| Related | 5K6C 5K6F 5K6G 5K6H 5K6I |
| Descriptor | Fusion glycoprotein F0, 2-acetamido-2-deoxy-beta-D-glucopyranose, SULFATE ION, ... (4 entities in total) |
| Functional Keywords | respiratory syncytial virus, prefusion, vaccine, stabilized, viral protein |
| Biological source | Human respiratory syncytial virus A |
| Total number of polymer chains | 1 |
| Total formula weight | 50078.80 |
| Authors | Joyce, M.G.,Zhang, B.,Rundlet, E.J.,Mascola, J.R.,Kwong, P.D. (deposition date: 2016-05-24, release date: 2016-08-31, Last modification date: 2024-10-16) |
| Primary citation | Joyce, M.G.,Zhang, B.,Ou, L.,Chen, M.,Chuang, G.Y.,Druz, A.,Kong, W.P.,Lai, Y.T.,Rundlet, E.J.,Tsybovsky, Y.,Yang, Y.,Georgiev, I.S.,Guttman, M.,Lees, C.R.,Pancera, M.,Sastry, M.,Soto, C.,Stewart-Jones, G.B.,Thomas, P.V.,Van Galen, J.G.,Baxa, U.,Lee, K.K.,Mascola, J.R.,Graham, B.S.,Kwong, P.D. Iterative structure-based improvement of a fusion-glycoprotein vaccine against RSV. Nat.Struct.Mol.Biol., 23:811-820, 2016 Cited by PubMed Abstract: Structure-based design of vaccines, particularly the iterative optimization used so successfully in the structure-based design of drugs, has been a long-sought goal. We previously developed a first-generation vaccine antigen called DS-Cav1, comprising a prefusion-stabilized form of the fusion (F) glycoprotein, which elicits high-titer protective responses against respiratory syncytial virus (RSV) in mice and macaques. Here we report the improvement of DS-Cav1 through iterative cycles of structure-based design that significantly increased the titer of RSV-protective responses. The resultant second-generation 'DS2'-stabilized immunogens have their F subunits genetically linked, their fusion peptides deleted and their interprotomer movements stabilized by an additional disulfide bond. These DS2 immunogens are promising vaccine candidates with superior attributes, such as their lack of a requirement for furin cleavage and their increased antigenic stability against heat inactivation. The iterative structure-based improvement described here may have utility in the optimization of other vaccine antigens. PubMed: 27478931DOI: 10.1038/nsmb.3267 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.981 Å) |
Structure validation
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