8e15

A computationally stabilized hMPV F protein

spinqualitylabelsall models 8e15, resolution 2.41Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8e15 is a 2 chain structure with sequence from Escherichia virus T2 and Human metapneumovirus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.41Å Ligands: BMA, NAG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q8B9P0_9MONO Publication Abstract from PubMed 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. A general computational design strategy for stabilizing viral class I fusion proteins.,Gonzalez KJ, Huang J, Criado MF, Banerjee A, Tompkins SM, Mousa JJ, Strauch EM Nat Commun. 2024 Feb 13;15(1):1335. doi: 10.1038/s41467-024-45480-z. PMID:38351001 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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