5WSN

Structure of Japanese encephalitis virus

5WSN の概要

• エントリーDOI: 10.2210/pdb5wsn/pdb
• EMDBエントリー: 6685
• 分子名称: E protein, M protein (2 entities in total)
• 機能のキーワード: japanese encephalitis virus, viral entry, flavivirus, neurotropism, virus
• 由来する生物種: Japanese encephalitis virus; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 185277.52

構造登録者

Wang, X.,Zhu, L.,Li, S.,Yuan, S.,Qin, C.,Fry, E.E.,Stuart, I.D.,Rao, Z. (登録日: 2016-12-07, 公開日: 2017-05-17, 最終更新日: 2024-10-23)

主引用文献

Wang, X.,Li, S.H.,Zhu, L.,Nian, Q.G.,Yuan, S.,Gao, Q.,Hu, Z.,Ye, Q.,Li, X.F.,Xie, D.Y.,Shaw, N.,Wang, J.,Walter, T.S.,Huiskonen, J.T.,Fry, E.E.,Qin, C.F.,Stuart, D.I.,Rao, Z.
Near-atomic structure of Japanese encephalitis virus reveals critical determinants of virulence and stability
Nat Commun, 8:14-14, 2017

PubMed Abstract: Although several different flaviviruses may cause encephalitis, Japanese encephalitis virus is the most significant, being responsible for thousands of deaths each year in Asia. The structural and molecular basis of this encephalitis is not fully understood. Here, we report the cryo-electron microscopy structure of mature Japanese encephalitis virus at near-atomic resolution, which reveals an unusual "hole" on the surface, surrounded by five encephalitic-specific motifs implicated in receptor binding. Glu138 of E, which is highly conserved in encephalitic flaviviruses, maps onto one of these motifs and is essential for binding to neuroblastoma cells, with the E138K mutation abrogating the neurovirulence and neuroinvasiveness of Japanese encephalitis virus in mice. We also identify structural elements modulating viral stability, notably Gln264 of E, which, when replaced by His264 strengthens a hydrogen-bonding network, leading to a more stable virus. These studies unveil determinants of neurovirulence and stability in Japanese encephalitis virus, opening up new avenues for therapeutic interventions against neurotropic flaviviruses.Japanese encephalitis virus (JEV) is a Flavivirus responsible for thousands of deaths every year for which there are no specific anti-virals. Here, Wang et al. report the cryo-EM structure of mature JEV at near-atomic resolution and identify structural elements that modulate stability and virulence.

PubMed: 28446752
DOI: 10.1038/s41467-017-00024-6

実験手法

ELECTRON MICROSCOPY (4.3 Å)