Interaction of adenovirus VA RNAl with the protein kinase DAI: nonequivalence of binding and function

Mellits, K. H., Kostura, M., Mathews, M. B. (June 1990) Interaction of adenovirus VA RNAl with the protein kinase DAI: nonequivalence of binding and function. Cell, 61 (5). pp. 843-52. ISSN 0092-8674 (Print)0092-8674 (Linking)

Abstract

Adenovirus VA RNAL maintains protein synthesis by preventing activation of the double-stranded RNA (dsRNA)-dependent protein kinase DAI. There appears to be a single binding site for dsRNA on DAI, and this site is blocked by VA RNAl. VA RNAl binds to purified DAI and can be cross-linked to the enzyme by UV irradiation. To determine the relationship between DAI binding and VA RNAl structure and function, we examined the binding abilities of wild-type and mutant VA RNAs. In several cases, the ability to bind DAI efficiently in vitro did not correlate with function in vivo. Secondary structure analysis suggested that efficient binding requires an apical stem-loop structure, whereas inhibition of DAI activation requires the central domain of the VA RNA molecule. We propose that the duplex stem permits VA RNA to interact with the dsRNA binding site on DAI and inhibits activation by juxtaposing the central domain of the RNA with the enzyme's active site.

Item Type: Paper
Uncontrolled Keywords: Adenoviruses, Human/*genetics Base Sequence Enzyme Activation/physiology Immunosorbent Techniques Molecular Sequence Data Mutation Nucleic Acid Conformation Protein Binding Protein Kinases/*metabolism RNA, Viral/genetics/*metabolism Structure-Activity Relationship Ultraviolet Rays eIF-2 Kinase
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > RNAi
organism description > virus > adenovirus
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > kinase
CSHL Authors:
Communities: CSHL labs
Depositing User: Matt Covey
Date: 1 June 1990
Date Deposited: 29 Mar 2016 16:08
Last Modified: 29 Mar 2016 16:08
Related URLs:
URI: https://repository.cshl.edu/id/eprint/32301

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