5X8Y

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


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.82 Å
  • R-Value Free: 0.260 
  • R-Value Work: 0.210 
  • R-Value Observed: 0.215 

wwPDB Validation   3D Report Full Report


This is version 1.1 of the entry. See complete history


Literature

A Mutation Identified in Neonatal Microcephaly Destabilizes Zika Virus NS1 Assembly in Vitro

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.

(2017) Sci Rep 7: 42580-42580

  • DOI: https://doi.org/10.1038/srep42580
  • Primary Citation of Related Structures:  
    5X8Y

  • 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 172-352 , 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.


  • Organizational Affiliation

    School of Life Sciences, Tianjin University, Tianjin 300072, People's Republic of China.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
ZIKV NS1
A, B
185Zika virusMutation(s): 0 
UniProt
Find proteins for A0A0U4DG08 (Zika virus)
Explore A0A0U4DG08 
Go to UniProtKB:  A0A0U4DG08
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupA0A0U4DG08
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.82 Å
  • R-Value Free: 0.260 
  • R-Value Work: 0.210 
  • R-Value Observed: 0.215 
  • Space Group: C 2 2 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 63.934α = 90
b = 100.808β = 90
c = 110.72γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
HKL-2000data reduction
HKL-2000data scaling
PHASERphasing

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Key Basic Research Program of ChinaChina2015CB859800, 2014CB542800
National Natural Science Foundation of ChinaChina31528006, 31470730

Revision History  (Full details and data files)

  • Version 1.0: 2017-05-17
    Type: Initial release
  • Version 1.1: 2023-11-22
    Changes: Data collection, Database references, Refinement description