title: A putative ATPase mediates RNA transcription and capping in a dsRNA virus.
abstract: mRNA transcription in dsRNA viruses is a highly regulated process but the mechanism of this regulation is not known. Here, by nucleoside triphosphatase (NTPase) assay and comparisons of six high-resolution (2.9-3.1 Å) cryo-electron microscopy structures of cytoplasmic polyhedrosis virus with bound ligands, we show that the large sub-domain of the guanylyltransferase (GTase) domain of the turret protein (TP) also has an ATP-binding site and is likely an ATPase. S-adenosyl-L-methionine (SAM) acts as a signal and binds the methylase-2 domain of TP to induce conformational change of the viral capsid, which in turn activates the putative ATPase. ATP binding/hydrolysis leads to an enlarged capsid for efficient mRNA synthesis, an open GTase domain for His217-mediated guanylyl transfer, and an open methylase-1 domain for SAM binding and methyl transfer. Taken together, our data support a role of the putative ATPase in mediating the activation of mRNA transcription and capping within the confines of the virus.
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, United States.
authors.forename: Xuekui
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, United States.
authors.forename: Jiansen
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, United States.
authors.forename: Jingchen
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, United States.
authors.forename: Z Hong
authors.initials: ZH
authors.lastname: Zhou
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism*; D020285:Cryoelectron Microscopy; D012330:RNA, Double-Stranded / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D012367:RNA, Viral / Q000378:metabolism*; D012087:Reoviridae / Q000201:enzymology* / Q000235:genetics* / Q000648:ultrastructure; D014158:Transcription, Genetic; D014764:Viral Proteins / Q000378:metabolism
chemical_list: D012330:RNA, Double-Stranded; D012333:RNA, Messenger; D012367:RNA, Viral; D014764:Viral Proteins; D000251:Adenosine Triphosphatases
keywords: allosteric regulation; biochemistry; biophysics; conformational changes; histidine-mediated guanylyl transfer; structural biology; viral ATPase