8ygt

Cryo-EM structure of simian rotavirus SA11 VP4 in complex with nAb 7H13-I54G mutant (left side)

spinqualitylabelsall models 8ygt, resolution 3.01Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8ygt is a 4 chain structure with sequence from Mus musculus and Rotavirus A. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.01Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A5J6BC68_9REOV Publication Abstract from PubMed Broadly neutralizing antibodies (bNAbs) could offer escape-tolerant and lasting protection against viral infections and therefore guide development of broad-spectrum vaccines. The increasing challenge posed by viral evolution and immune evasion intensifies the importance of the discovery of bNAbs and their underlying neutralization mechanism. Here, focusing on the pivotal viral protein VP4 of rotavirus (RV), we identify a potent bNAb, 7H13, exhibiting broad-spectrum neutralization across diverse RV genotypes and demonstrating strong prevention of virus infection in female mice. A combination of time-resolved cryo-electron microscopy (cryo-EM) and in situ cryo-electron tomography (cryo-ET) analysis reveals a counterintuitive dynamic process of virus inactivation, in which 7H13 asymmetrically binds to a conserved epitope in the capsid-proximal aspect of VP4, triggers a conformational switch in a critical residue-F418-thereby disrupts the meta-stable conformation of VP4 essential for normal viral infection. Structure-guided mutagenesis corroborates the essential role of the 7H13 heavy chain I54 in activating F418 switch and destabilizing VP4. These findings define an atypical NAbs' neutralization mechanism and reveal a potential type of virus vulnerable site for universal vaccine and therapeutics design. A single residue switch mediates the broad neutralization of Rotaviruses.,Huang Y, Song F, Zeng Y, Sun H, Sheng R, Wang X, Liu L, Luo G, Jiang Y, Chen Y, Zhang M, Zhang S, Gu Y, Yu H, Li S, Li T, Zheng Q, Ge S, Zhang J, Xia N Nat Commun. 2025 Jan 20;16(1):838. doi: 10.1038/s41467-025-56114-3. PMID:39833145 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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