title: The flaviviral methyltransferase is a substrate of Casein Kinase 1.
abstract: Serine/Threonine phosphorylation of the nonstructural protein 5 (NS5) is a conserved feature of flaviviruses, but the identity and function(s) of the responsible kinase(s) remain unknown. Serine 56 in the methyltransferase domain of NS5 can be phosphorylated intracellularly, is conserved in all flaviviruses, and is a critical residue in the catalytic mechanism. A negative charge at this residue inactivates the 2'-0 methyltransferase activity necessary to form a 5' cap structure of the viral RNA. Here we show pharmacologic inhibition of Casein Kinase 1 (CK1) suppresses yellow fever virus (YFV) production. We also demonstrate the alpha isoform of Casein Kinase 1 (CK1alpha), a kinase previously identified as phosphorylating Hepatitis C Virus NS5A protein, also phosphorylates serine 56 of YFV methyltransferase. Overall these results suggest CK1 activity can influence flaviviral replication.
authors.affiliation: Department of Medicine, University of Wisconsin-Madison, 1550 Linden Drive, Madison, WI 53706, United States.
authors.forename: Dipankar
authors.initials: D
authors.lastname: Bhattacharya
authors.forename: Israrul H
authors.initials: IH
authors.lastname: Ansari
authors.forename: Rob
authors.initials: R
authors.lastname: Striker
mesh_terms: D047389:Casein Kinase I / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D005416:Flavivirus / Q000737:chemistry / Q000201:enzymology / Q000502:physiology; D018177:Flavivirus Infections / Q000201:enzymology*; D006801:Humans; D008780:Methyltransferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D013379:Substrate Specificity; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication; D015005:Yellow fever virus / Q000737:chemistry / Q000201:enzymology* / Q000502:physiology
chemical_list: D014764:Viral Proteins; D008780:Methyltransferases; D047389:Casein Kinase I