8E15
A computationally stabilized hMPV F protein
Summary for 8E15
| Entry DOI | 10.2210/pdb8e15/pdb |
| Descriptor | F2 protein, F1 protein with Fibritin peptide, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total) |
| Functional Keywords | human metapneumovirus, fusion protein, computational stabilization, viral protein |
| Biological source | Human metapneumovirus More |
| Total number of polymer chains | 2 |
| Total formula weight | 58715.36 |
| Authors | Huang, J.,Gonzalez, K.,Mousa, J.,Strauch, E. (deposition date: 2022-08-09, release date: 2023-04-12, Last modification date: 2024-07-24) |
| Primary citation | Gonzalez, K.J.,Huang, J.,Criado, M.F.,Banerjee, A.,Tompkins, S.M.,Mousa, J.J.,Strauch, E.M. A general computational design strategy for stabilizing viral class I fusion proteins. Nat Commun, 15:1335-1335, 2024 Cited by PubMed Abstract: Many pathogenic viruses rely on class I fusion proteins to fuse their viral membrane with the host cell membrane. To drive the fusion process, class I fusion proteins undergo an irreversible conformational change from a metastable prefusion state to an energetically more stable postfusion state. Mounting evidence underscores that antibodies targeting the prefusion conformation are the most potent, making it a compelling vaccine candidate. Here, we establish a computational design protocol that stabilizes the prefusion state while destabilizing the postfusion conformation. With this protocol, we stabilize the fusion proteins of the RSV, hMPV, and SARS-CoV-2 viruses, testing fewer than a handful of designs. The solved structures of these designed proteins from all three viruses evidence the atomic accuracy of our approach. Furthermore, the humoral response of the redesigned RSV F protein compares to that of the recently approved vaccine in a mouse model. While the parallel design of two conformations allows the identification of energetically sub-optimal positions for one conformation, our protocol also reveals diverse molecular strategies for stabilization. Given the clinical significance of viruses using class I fusion proteins, our algorithm can substantially contribute to vaccine development by reducing the time and resources needed to optimize these immunogens. PubMed: 38351001DOI: 10.1038/s41467-024-45480-z PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.41 Å) |
Structure validation
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