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Biophys J. 2015 Feb 3;108(3):748-57. doi: 10.1016/j.bpj.2014.12.014.

Structural analysis of adenovirus VAI RNA defines the mechanism of inhibition of PKR.

Author information

1
Department of Molecular and Cell Biology, University of Connecticut, Storrs, Connecticut.
2
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.

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.

PMID:
25650941
PMCID:
PMC4317563
DOI:
10.1016/j.bpj.2014.12.014
[Indexed for MEDLINE]
Free PMC Article

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