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. Overall, our results will contribute to future studies on ZIKV infection and the development of inhibitors of ZIKV replication.
authors.affiliation: Department of Biochemistry and Biophysics, Texas A&M University, College Station, Texas 77843, USA.
authors.forename: Baoyu
authors.initials: B
authors.lastname: Zhao
authors.affiliation: Department of Molecular and Cellular Biochemistry, Indiana University, Bloomington, Indiana 47405, USA.
authors.forename: Guanghui
authors.initials: G
authors.lastname: Yi
authors.affiliation: Department of Biochemistry and Biophysics, Texas A&M University, College Station, Texas 77843, USA.
authors.forename: Fenglei
authors.initials: F
authors.lastname: Du
authors.affiliation: Department of Molecular and Cellular Biochemistry, Indiana University, Bloomington, Indiana 47405, USA.
authors.forename: Yin-Chih
authors.initials: YC
authors.lastname: Chuang
authors.affiliation: Department of Molecular and Cellular Biochemistry, Indiana University, Bloomington, Indiana 47405, USA.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Vaughan
authors.affiliation: Molecular Biophysics and Integrated Bioimaging, Berkeley Center for Structural Biology, 1 Cyclotron Road, Lawrence Berkeley National Lab, Berkeley 94720, USA.
authors.forename: Banumathi
authors.initials: B
authors.lastname: Sankaran
authors.affiliation: Department of Molecular and Cellular Biochemistry, Indiana University, Bloomington, Indiana 47405, USA.
authors.forename: C Cheng
authors.initials: CC
authors.lastname: Kao
authors.affiliation: Department of Biochemistry and Biophysics, Texas A&M University, College Station, Texas 77843, USA.
authors.forename: Pingwei
authors.initials: P
authors.lastname: Li
mesh_terms: D018360:Crystallography, X-Ray; D008780:Methyltransferases / Q000378:metabolism; D011487:Protein Conformation; D012315:RNA Caps; D012324:RNA-Dependent RNA Polymerase / Q000378:metabolism; D013379:Substrate Specificity; D017361:Viral Nonstructural Proteins / Q000737:chemistry* / Q000378:metabolism*; D014779:Virus Replication; D000071244:Zika Virus / Q000378:metabolism* / Q000502:physiology
chemical_list: C096041:NS5 protein, flavivirus; D012315:RNA Caps; D017361:Viral Nonstructural Proteins; D008780:Methyltransferases; D012324:RNA-Dependent RNA Polymerase