7SEJ
Structure-based design of prefusion-stabilized human metapneumovirus fusion proteins
Summary for 7SEJ
Entry DOI | 10.2210/pdb7sej/pdb |
Descriptor | Fusion glycoprotein F2 subunit, Fusion glycoprotein F1 subunit, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total) |
Functional Keywords | human metapneumovirus, fusion protein, viral protein |
Biological source | Human metapneumovirus More |
Total number of polymer chains | 4 |
Total formula weight | 121828.56 |
Authors | Hsieh, C.-L.,Rush, S.A.,McLellan, J.S. (deposition date: 2021-09-30, release date: 2022-02-09, Last modification date: 2024-10-23) |
Primary citation | Hsieh, C.L.,Rush, S.A.,Palomo, C.,Chou, C.W.,Pickens, W.,Mas, V.,McLellan, J.S. Structure-based design of prefusion-stabilized human metapneumovirus fusion proteins. Nat Commun, 13:1299-1299, 2022 Cited by PubMed Abstract: The human metapneumovirus (hMPV) fusion (F) protein is essential for viral entry and is a key target of neutralizing antibodies and vaccine development. The prefusion conformation is thought to be the optimal vaccine antigen, but previously described prefusion F proteins expressed poorly and were not well stabilized. Here, we use structures of hMPV F to guide the design of 42 variants containing stabilizing substitutions. Through combinatorial addition of disulfide bonds, cavity-filling substitutions, and improved electrostatic interactions, we describe a prefusion-stabilized F protein (DS-CavEs2) that expresses at 15 mg/L and has a melting temperature of 71.9 °C. Crystal structures of two prefusion-stabilized hMPV F variants reveal that antigenic surfaces are largely unperturbed. Importantly, immunization of mice with DS-CavEs2 elicits significantly higher neutralizing antibody titers against hMPV A1 and B1 viruses than postfusion F. The improved properties of DS-CavEs2 will advance the development of hMPV vaccines and the isolation of therapeutic antibodies. PubMed: 35288548DOI: 10.1038/s41467-022-28931-3 PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (2.51 Å) |
Structure validation
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