8w3q

Crystal structure of prefusion-stabilized hMPV F protein UFCM1-P2-iSS

spinqualitylabelsall models 8w3q, resolution 5.99Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8w3q is a 1 chain structure with sequence from Human metapneumovirus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 5.99Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed 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(2)-F(1) 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 O 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. Rational design of uncleaved prefusion-closed trimer vaccines for human respiratory syncytial virus and metapneumovirus.,Lee YZ, Han J, Zhang YN, Ward G, Braz Gomes K, Auclair S, Stanfield RL, He L, Wilson IA, Zhu J Nat Commun. 2024 Nov 16;15(1):9939. doi: 10.1038/s41467-024-54287-x. PMID:39550381 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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