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Title: Structure and function of the Zika virus full-length NS5 protein

Abstract

The recent outbreak of Zika virus (ZIKV) has infected over 1 million people in over 30 countries. ZIKV replicates its RNA genome using virally encoded replication proteins. Nonstructural protein 5 (NS5) contains a methyltransferase for RNA capping and a polymerase for viral RNA synthesis. Here we report the crystal structures of full-length NS5 and its polymerase domain at 3.0 Å resolution. The NS5 structure has striking similarities to the NS5 protein of the related Japanese encephalitis virus. The methyltransferase contains in-line pockets for substrate binding and the active site. Key residues in the polymerase are located in similar positions to those of the initiation complex for the hepatitis C virus polymerase. The polymerase conformation is affected by the methyltransferase, which enables a more efficiently elongation of RNA synthesis in vitro. Altogether, our results will contribute to future studies on ZIKV infection and the development of inhibitors of ZIKV replication.

Authors:
 [1];  [2];  [1];  [2];  [2];  [3];  [2];  [1]
  1. Texas A & M Univ., College Station, TX (United States)
  2. Indiana Univ., Bloomington, IN (United States)
  3. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Publication Date:
Research Org.:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22)
OSTI Identifier:
1409432
DOE Contract Number:  
AC02-05CH11231
Resource Type:
Journal Article
Journal Name:
Nature Communications
Additional Journal Information:
Journal Volume: 8; Journal ID: ISSN 2041-1723
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES

Citation Formats

Zhao, Baoyu, Yi, Guanghui, Du, Fenglei, Chuang, Yin -Chih, Vaughan, Robert C., Sankaran, Banumathi, Kao, C. Cheng, and Li, Pingwei. Structure and function of the Zika virus full-length NS5 protein. United States: N. p., 2017. Web. doi:10.1038/ncomms14762.
Zhao, Baoyu, Yi, Guanghui, Du, Fenglei, Chuang, Yin -Chih, Vaughan, Robert C., Sankaran, Banumathi, Kao, C. Cheng, & Li, Pingwei. Structure and function of the Zika virus full-length NS5 protein. United States. doi:10.1038/ncomms14762.
Zhao, Baoyu, Yi, Guanghui, Du, Fenglei, Chuang, Yin -Chih, Vaughan, Robert C., Sankaran, Banumathi, Kao, C. Cheng, and Li, Pingwei. Mon . "Structure and function of the Zika virus full-length NS5 protein". United States. doi:10.1038/ncomms14762. https://www.osti.gov/servlets/purl/1409432.
@article{osti_1409432,
title = {Structure and function of the Zika virus full-length NS5 protein},
author = {Zhao, Baoyu and Yi, Guanghui and Du, Fenglei and Chuang, Yin -Chih and Vaughan, Robert C. and Sankaran, Banumathi and Kao, C. Cheng and Li, Pingwei},
abstractNote = {The recent outbreak of Zika virus (ZIKV) has infected over 1 million people in over 30 countries. ZIKV replicates its RNA genome using virally encoded replication proteins. Nonstructural protein 5 (NS5) contains a methyltransferase for RNA capping and a polymerase for viral RNA synthesis. Here we report the crystal structures of full-length NS5 and its polymerase domain at 3.0 Å resolution. The NS5 structure has striking similarities to the NS5 protein of the related Japanese encephalitis virus. The methyltransferase contains in-line pockets for substrate binding and the active site. Key residues in the polymerase are located in similar positions to those of the initiation complex for the hepatitis C virus polymerase. The polymerase conformation is affected by the methyltransferase, which enables a more efficiently elongation of RNA synthesis in vitro. Altogether, our results will contribute to future studies on ZIKV infection and the development of inhibitors of ZIKV replication.},
doi = {10.1038/ncomms14762},
journal = {Nature Communications},
issn = {2041-1723},
number = ,
volume = 8,
place = {United States},
year = {2017},
month = {3}
}

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