5X8Y

A Mutation identified in Neonatal Microcephaly Destabilizes Zika Virus NS1 Assembly in vitro

5X8Y の概要

• エントリーDOI: 10.2210/pdb5x8y/pdb
• 分子名称: ZIKV NS1 (2 entities in total)
• 機能のキーワード: zika virus, ns1, viral protein
• 由来する生物種: Zika virus
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 42374.11

構造登録者

Wang, D.,Chen, C.,Liu, S.,Zhou, H.,Yang, K.,Zhao, Q.,Ji, X.,Chen, C.,Xie, W.,Wang, Z.,Mi, L.Z.,Yang, H. (登録日: 2017-03-03, 公開日: 2017-05-17, 最終更新日: 2024-10-23)

主引用文献

Wang, D.,Chen, C.,Liu, S.,Zhou, H.,Yang, K.,Zhao, Q.,Ji, X.,Chen, C.,Xie, W.,Wang, Z.,Mi, L.Z.,Yang, H.
A Mutation Identified in Neonatal Microcephaly Destabilizes Zika Virus NS1 Assembly in Vitro
Sci Rep, 7:42580-42580, 2017

PubMed Abstract: An unprecedented epidemic of Zika virus (ZIKV) infection had spread to South and Central America. ZIKV infection was recently confirmed by CDC (the Centers for Disease Control and Prevention) to cause neonatal microcephaly, which posed a significant public health emergency of international concern. No specific vaccines or drugs are currently available to fight ZIKV infection. ZIKV nonstructural protein 1 (NS1) plays an essential role in viral replication and immune evasion. We determined the crystal structure of ZIKV NS1, which forms a head-to-head, symmetric dimer with a unique 14-stranded β-ladder conserved among flaviviruses. The assembly of the β-ladder dimer is concentration dependent. Strikingly, one pathogenic mutation T233A (NCBI accession no. KU527068), found in the brain tissue of infected fetus with neonatal microcephaly, is located at the dimer interface. Thr233, a unique residue found in ZIKV but not in other flaviviruses, organizes a central hydrogen bonding network at NS1 dimer interface. Mutation of Thr233 to Ala disrupts this elaborated interaction network, and destabilizes the NS1 dimeric assembly in vitro. In addition, our structural comparison of epitopes for protective antibody 22NS1, targeting West Nile Virus NS1, could potentially be valuable in understanding its anti-virus specificities and in the development of antibodies against ZIKV.

PubMed: 28198446
DOI: 10.1038/srep42580

実験手法

X-RAY DIFFRACTION (2.817 Å)