5ywf | pdb_00005ywf
Crystal structure of 2H4 Fab
Structural highlights
Publication Abstract from PubMedJapanese encephalitis virus (JEV), closely related to dengue, Zika, yellow fever and West Nile viruses, remains neglected and not well characterized (1) . JEV is the leading causative agent of encephalitis, and is responsible for thousands of deaths each year in Asia. Humoral immunity is essential for protecting against flavivirus infections and passive immunization has been demonstrated to be effective in curing disease(2,3). Here, we demonstrate that JEV-specific monoclonal antibodies, 2F2 and 2H4, block attachment of the virus to its receptor and also prevent fusion of the virus. Neutralization of JEV by these antibodies is exceptionally potent and confers clear therapeutic benefit in mouse models. A single 20 mug dose of these antibodies resulted in 100% survival and complete clearance of JEV from the brains of mice. The 4.7 A and 4.6 A resolution cryo-electron microscopy structures of JEV-2F2-Fab and JEV-2H4-Fab complexes, together with the crystal structure of 2H4 Fab and our recent near-atomic structure of JEV (4) , unveil the nature and location of epitopes targeted by the antibodies. Both 2F2 and 2H4 Fabs bind quaternary epitopes that span across three adjacent envelope proteins. Our results provide a structural and molecular basis for the application of 2F2 and 2H4 to treat JEV infection. Structural basis for neutralization of Japanese encephalitis virus by two potent therapeutic antibodies.,Qiu X, Lei Y, Yang P, Gao Q, Wang N, Cao L, Yuan S, Huang X, Deng Y, Ma W, Ding T, Zhang F, Wu X, Hu J, Liu SL, Qin C, Wang X, Xu Z, Rao Z Nat Microbiol. 2018 Mar;3(3):287-294. doi: 10.1038/s41564-017-0099-x. Epub 2018, Jan 29. PMID:29379207[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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