8W3O
Crystal structure of prefusion-stabilized RSV F protein UFCR3-GDQ
This is a non-PDB format compatible entry.
Summary for 8W3O
| Entry DOI | 10.2210/pdb8w3o/pdb |
| Descriptor | prefusion-stabilized RSV F protein UFCR3-GDQ, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total) |
| Functional Keywords | respiratory syncytial virus, glycoprotein, prefusion vaccine, stabilized, viral protein |
| Biological source | Human respiratory syncytial virus A2 |
| Total number of polymer chains | 1 |
| Total formula weight | 56225.18 |
| Authors | Lee, Y.Z.,Stanfield, R.L.,Wilson, I.A.,Zhu, J. (deposition date: 2024-02-22, release date: 2025-01-15) |
| Primary citation | Lee, Y.Z.,Han, J.,Zhang, Y.N.,Ward, G.,Braz Gomes, K.,Auclair, S.,Stanfield, R.L.,He, L.,Wilson, I.A.,Zhu, J. Rational design of uncleaved prefusion-closed trimer vaccines for human respiratory syncytial virus and metapneumovirus. Nat Commun, 15:9939-9939, 2024 Cited by PubMed Abstract: Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) cause human respiratory diseases and are major targets for vaccine development. In this study, we design uncleaved prefusion-closed (UFC) trimers for the fusion protein (F) of both viruses by examining mutations critical to F metastability. For RSV, we assess four previous prefusion F designs, including the first and second generations of DS-Cav1, SC-TM, and 847A. We then identify key mutations that can maintain prefusion F in a native-like, closed trimeric form (up to 76%) without introducing any interprotomer disulfide bond. For hMPV, we develop a stable UFC trimer with a truncated F-F linkage and an interprotomer disulfide bond. Dozens of UFC constructs are characterized by negative-stain electron microscopy (nsEM), x-ray crystallography (11 RSV-F structures and one hMPV-F structure), and antigenic profiling. Using an optimized RSV-F UFC trimer as bait, we identify three potent RSV neutralizing antibodies (NAbs) from a phage-displayed human antibody library, with a public NAb lineage targeting sites Ø and V and two cross-pneumovirus NAbs recognizing site III. In mouse immunization, rationally designed RSV-F and hMPV-F UFC trimers induce robust antibody responses with high neutralizing titers. Our study provides a foundation for future prefusion F-based RSV and hMPV vaccine development. PubMed: 39550381DOI: 10.1038/s41467-024-54287-x PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.31 Å) |
Structure validation
Download full validation report
