5YWF

Crystal structure of 2H4 Fab

5YWF の概要

• エントリーDOI: 10.2210/pdb5ywf/pdb
• 分子名称: 2H4 light chain, 2H4 heavy chain (3 entities in total)
• 機能のキーワード: flaviviruses, viral encephalitis, neutralizing monoclonal antibodies, structural analysis, viral entry, immune system
• 由来する生物種: Mus musculus; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 94355.22

構造登録者

Qiu, X.,Lei, Y.,Yang, P.,Gao, Q.,Wang, N.,Cao, L.,Wang, X.,Xu, Z.K.,Rao, Z. (登録日: 2017-11-29, 公開日: 2018-03-21)

主引用文献

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, S.L.,Qin, C.,Wang, X.,Xu, Z.,Rao, Z.
Structural basis for neutralization of Japanese encephalitis virus by two potent therapeutic antibodies
Nat Microbiol, 3:287-294, 2018

PubMed Abstract: Japanese encephalitis virus (JEV), closely related to dengue, Zika, yellow fever and West Nile viruses, remains neglected and not well characterized . 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. 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 μg dose of these antibodies resulted in 100% survival and complete clearance of JEV from the brains of mice. The 4.7 Å and 4.6 Å 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 , 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.

PubMed: 29379207
DOI: 10.1038/s41564-017-0099-x

実験手法

X-RAY DIFFRACTION (2.206 Å)