Journal
JOURNAL OF STRUCTURAL BIOLOGY
Volume 185, Issue 1, Pages 48-57Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.jsb.2013.11.007
Keywords
Adenovirus; dsRNA; PKR; Protein-RNA interactions; Small angle X-ray scattering; VA(I) RNA; in silico structure determination
Funding
- University of Manitoba Faculty of Science and Graduate Studies
- University of Manitoba Graduate Fellowship
- Natural Sciences and Engineering Research Council of Canada [371372-2010]
- Manitoba Health Research Council
- Foundation for Polish Science (FNP) [TEAM/2009-4/2]
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Adenovirus virus-associated RNA (VA(I)) provides protection against the host antiviral response in part by inhibiting the interferon-induced double stranded RNA-activated protein kinase (PKR). VA(I) consists of three base-paired regions; the apical stem responsible for the interaction with double-stranded RNA binding motifs (dsRBMs) of PKR, the central stem required for inhibition, and the terminal stem. The solution conformation of VA(I) and VA(I) lacking the terminal stem were determined using SAXS that suggested extended conformations that are in agreement with their secondary structures. Solution conformations of VA(I) lacking the terminal stem in complex with the dsRBMs of PKR indicated that the apical stem interacts with both dsRNA-binding motifs whereas the central stem does not. Hydrodynamic properties calculated from ab initio models were compared to experimentally determined parameters for model validation. Furthermore, SAXS envelopes were used as a constraint for the in silico modeling of tertiary structure for RNA and RNA protein complex. Finally, full-length PKR was also studied, but concentration-dependent changes in hydrodynamic parameters prevented ab initio shape determination. Taken together, results provide an improved structural framework that further our understanding of the role VA(I) plays in evading host innate immune responses. (C) 2013 Elsevier Inc. All rights reserved.
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