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

• Published in: Nature communications Vol. 8; no. 1; pp. 14762 - 9
• Main Authors: Zhao, Baoyu, Yi, Guanghui, Du, Fenglei, Chuang, Yin-Chih, Vaughan, Robert C., Sankaran, Banumathi, Kao, C. Cheng, Li, Pingwei
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 27.03.2017; Nature Publishing Group; Nature Portfolio
• Subjects: 60 APPLIED LIFE SCIENCES; 631/326/596/2148; 631/45/535/1266; 82/58; 82/80; BASIC BIOLOGICAL SCIENCES; Biochemistry; Biophysics; Crystal structure; Crystallography, X-Ray; Encephalitis; Fingers & toes; Genomes; Humanities and Social Sciences; Ligands; Methyltransferases - metabolism; multidisciplinary; Protein Conformation; Proteins; RNA Caps; RNA polymerase; RNA Replicase - metabolism; Science; Science (multidisciplinary); Substrate Specificity; Vector-borne diseases; Viral Nonstructural Proteins - chemistry; Viral Nonstructural Proteins - metabolism; Virus Replication; Zika virus; Zika Virus - metabolism; Zika Virus - physiology; Indiana; United States > US; Texas
• DOI: 10.1038/ncomms14762
• ISSN: 2041-1723

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 . Overall, our results will contribute to future studies on ZIKV infection and the development of inhibitors of ZIKV replication. Zika virus infection can cause human birth defects and Guillain-Barré syndrome. Here the authors present the structures of the full-length nonstructural protein 5 and its RNA-dependent RNA polymerase domain of Zika virus, which are targets for inhibitors of virus replication.