title: Structural analysis of adenovirus VAI RNA defines the mechanism of inhibition of PKR.
abstract: Protein kinase R (PKR) is activated by dsRNA produced during virus replication and plays a major role in the innate immunity response to virus infection. In response, viruses have evolved multiple strategies to evade PKR. Adenovirus virus-associated RNA-I (VAI) is a short, noncoding transcript that functions as an RNA decoy to sequester PKR in an inactive state. VAI consists of an apical stem-loop, a highly structured central domain, and a terminal stem. Chemical probing and mutagenesis demonstrate that the central domain is stabilized by a pseudoknot. A structural model of VAI was obtained from constraints derived from chemical probing and small angle x-ray scattering (SAXS) measurements. VAI adopts a flat, extended conformation with the apical and terminal stems emanating from a protuberance in the center. This model reveals how the apical stem and central domain assemble to produce an extended duplex that is precisely tuned to bind a single PKR monomer with high affinity, thereby inhibiting activation of PKR by viral dsRNA.
authors: Department of Molecular and Cell Biology, University of Connecticut, Storrs, Connecticut.
authors: Katherine
authors: K
authors: Launer-Felty
authors: Department of Molecular and Cell Biology, University of Connecticut, Storrs, Connecticut.
authors: C Jason
authors: CJ
authors: Wong
authors: Department of Molecular and Cell Biology, University of Connecticut, Storrs, Connecticut; Department of Chemistry, University of Connecticut, Storrs, Connecticut. Electronic address: james.cole@uconn.edu.
authors: James L
authors: JL
authors: Cole
mesh_terms: D001483:Base Sequence; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012367:RNA, Viral / Q000737:chemistry* / Q000235:genetics; D053838:Scattering, Small Angle; D014961:X-Ray Diffraction; D019892:eIF-2 Kinase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism
chemical_list: D012367:RNA, Viral; C052835:adenovirus associated RNA; D019892:eIF-2 Kinase
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