6lht | pdb_00006lht

Localized reconstruction of coxsackievirus A16 mature virion in complex with Fab 18A7

Loading... Status: waiting for Mol* initialization Structural highlights 6lht is a 7 chain structure with sequence from Coxsackievirus a16 and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: SPH Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Hand, foot, and mouth disease is a common childhood illness primarily caused by coxsackievirus A16 (CVA16), for which there are no current vaccines or treatments. We identify three CVA16-specific neutralizing monoclonal antibodies (nAbs) with therapeutic potential: 18A7, 14B10, and NA9D7. We present atomic structures of these nAbs bound to all three viral particle forms-the mature virion, A-particle, and empty particle-and show that each Fab can simultaneously occupy the mature virion. Additionally, 14B10 or NA9D7 provide 100% protection against lethal CVA16 infection in a neonatal mouse model. 18A7 binds to a non-conserved epitope present in all three particles, whereas 14B10 and NA9D7 recognize broad protective epitopes but only bind the mature virion. NA9D7 targets an immunodominant site, which may overlap the receptor-binding site. These findings indicate that CVA16 vaccines should be based on mature virions and that these antibodies could be used to discriminate optimal virion-based immunogens. Identification of Antibodies with Non-overlapping Neutralization Sites that Target Coxsackievirus A16.,He M, Xu L, Zheng Q, Zhu R, Yin Z, Zha Z, Lin Y, Yang L, Huang Y, Ye X, Li S, Hou W, Wu Y, Han J, Liu D, Li Z, Chen Z, Yu H, Que Y, Wang Y, Yan X, Zhang J, Gu Y, Zhou ZH, Cheng T, Li S, Xia N Cell Host Microbe. 2020 Feb 12;27(2):249-261.e5. doi: 10.1016/j.chom.2020.01.003., Epub 2020 Feb 5. PMID:32027857 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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