Identification of a Conserved Motif That Is Necessary for Binding of the Vaccinia Virus E3L Gene Products to Double-Stranded RNA

Chang, Hwai-Wen; Jacobs, Bertram L.

doi:10.1006/viro.1993.1292

Cited by 149 publications

(159 citation statements)

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“…Furthermore, dsRBD-containing fragments bound poly(rI⅐rC) in the presence of up to 0.5 M NaCl. In this respect, the dsRBDs from human NDH II were comparable with other dsRBDs, such as those of the dsRNA-dependent protein kinase DAI (7), the dsRNA-specific adenosine deaminase DRADA (37), and the E3L protein from vaccinia viruses (12,38). For DAI it has been shown that its two N-terminal dsRBDs are responsible for specific binding to dsRNA.…”

Section: Discussionmentioning

confidence: 83%

“…Similar motifs are conserved among a group of dsRNA-binding proteins, such as dsRNA-dependent protein kinase (DAI) (7), dsRNA-specific adenosine deaminase (DRADA) (8), Escherichia coli RNase III (9), the Drosophila staufen protein, the Xenopus laevis RNA-binding protein Xlrbpa, the human transactivator region binding protein (10,11), and the vaccinia virus E3L protein (12). The carboxylterminal 100 amino acids of NDH II consist of a consecutive stretch of glycines that is regularly interrupted by either aromatic amino acids or arginine.…”

mentioning

confidence: 99%

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Domain Structure of Human Nuclear DNA Helicase II (RNA Helicase A)

Zhang¹,

Grosse²

1997

Journal of Biological Chemistry

108

125

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Full-length human nuclear DNA helicase II (NDH II) was cloned and overexpressed in a baculovirus-derived expression system. Recombinant NDH II unwound both DNA and RNA. Limited tryptic digestion produced active helicases with molecular masses of 130 and 100 kDa. The 130-kDa helicase missed a glycine-rich domain (RGG-box) at the carboxyl terminus, while the 100-kDa form missed both its double-stranded RNA binding domains (dsRBDs) at the amino terminus and its RGG-box. Hence, the dsRBDs and the RGG-box were dispensable for unwinding. On the other hand, the isolated DEXH core alone could neither hydrolyze ATP nor unwind nucleic acids. These enzymatic activities were not regained by fusing a complete COOH or NH 2 terminus to the helicase core. Hence, an active helicase required part of the NH 2 terminus, the DEXH core, and a C-terminal extension of the core. Both dsRBDs and the RGGbox were bacterially expressed as glutathione S-transferase fusion proteins. The two dsRBDs had a strong affinity to double-stranded RNA and cooperated upon RNA binding, while the RGG-box bound preferentially to single-stranded DNA. A model is suggested in which the flanking domains influence and regulate the unwinding properties of NDH II.Nuclear DNA helicase II (NDH II) 1 was originally isolated from calf thymus by assaying its DNA unwinding activity (1). Subsequently, it was shown that NDH II also contains RNA helicase activity (2). The cDNA sequence of NDH II (3) revealed a high homology to two previously known proteins, namely human RNA helicase A (4) and the Drosophila "maleless" protein (MLE) (5). From the cDNA sequences it was also deduced that the three proteins belong to the superfamily of DEXH helicases, all members of which possess seven conserved helicase motifs in the putative catalytically active core. The presence of the DEXH helicase core domain suggests a function in RNA and/or DNA unwinding for all three members of this superfamily. The core contains an ATP binding site with the consensus sequence GCGKT (A site) and FILDD (B site) in motif

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Section: Discussionmentioning

confidence: 83%

mentioning

confidence: 99%

Domain Structure of Human Nuclear DNA Helicase II (RNA Helicase A)

Zhang¹,

Grosse²

1997

Journal of Biological Chemistry

108

125

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“…To circumvent this response, viruses have evolved proteins that inhibit PKR function. One of these is the vaccinia virus IFN resistance gene E3L, which competitively inhibits PKR activity (7). Orthologues are found in most chordopoxviridae.…”

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confidence: 99%

“…However, the ability of the Z␣ domain to bind left-handed Z-DNA is essential for pathogenicity in mice (8,9). The RBM of E3L acts competitively to inhibit the activity of PKR and other proteins that contain RBMs (7,10,11). E3L also may act competitively against a group of host proteins that bind to the Z-conformation (12).…”

mentioning

confidence: 99%

A PKR-like eukaryotic initiation factor 2α kinase from zebrafish contains Z-DNA binding domains instead of dsRNA binding domains

Rothenburg

Deigendesch

Dittmar

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

157

196

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The double-stranded RNA (dsRNA)-dependent protein kinase (PKR) is induced as part of the IFN response in mammals and acts to shut down protein synthesis by the phosphorylation of eukaryotic initiation factor 2␣ (eIF2␣). In fish, a PKR-like kinase activity has been detected, but the enzyme responsible has eluded characterization. Here, we describe a PKR-like kinase from zebrafish. Phylogenetic analysis shows that the C-terminal kinase domain is more closely related to the kinase domain of PKR than to any of the other three known eIF2␣ kinases. Surprisingly, instead of the two dsRNA binding domains found at the N terminus of PKR, there are two Z␣ domains. Z␣ domains specifically bind dsDNA and RNA in the left-handed Z conformation, often with high affinity. They have been found previously in two other IFN-inducible proteins, the dsRNA editing enzyme, ADAR1, and Z-DNA binding protein 1 (ZBP1), as well as in the poxvirus virulence factor, E3L. This previously undescribed kinase, designated PKZ (protein kinase containing Z-DNA binding domains), is transcribed constitutively at low levels and is highly induced after injection of poly(inosinic)-poly(cytidylic) acid, which simulates viral infection. Binding of Z-DNA by the Z␣ domain of PKZ was demonstrated by circular dichroism. PKZ inhibits translation in transfected cells; site-directed mutagenesis indicates that this inhibition depends on its catalytic activity. Identification of a gene combining Z␣ domains with a PKR-like kinase domain strengthens the hypothesis that the ability to bind left-handed nucleic acid plays a role in the host response to viruses.E3L ͉ interferon response ͉ viral infection ͉ Z-RNA ͉ Z␣ domain

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“…The vaccinia virus E3L gene is an essential virulence gene that confers IFN resistance in cell culture of a broad range of hosts (Beattie et al, 1996;Langland and Jacobs, 2002). The E3L gene encodes a 190-amino-acid protein with a highly conserved, carboxyl-terminal, double-stranded RNA (dsRNA)-binding domain (Chang and Jacobs, 1993;Saunders and Barber, 2003). The dsRNA-binding domain has been shown to be required for both IFN resistance and broad-host-range phenotypes associated with the vaccinia virus (Chang et al, 1995).…”

Section: Vaccinia Virus E3l (E3l)mentioning

confidence: 99%

Silencing suppressors: viral weapons for countering host cell defenses

et al. 2011

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RNA silencing is a conserved eukaryotic pathway involved in the suppression of gene expression via sequence-specific interactions that are mediated by 21-23 nt RNA molecules. During infection, RNAi can act as an innate immune system to defend against viruses. As a counter-defensive strategy, silencing suppressors are encoded by viruses to inhibit various stages of the silencing process. These suppressors are diverse in sequence and structure and act via different mechanisms. In this review, we discuss whether RNAi is a defensive strategy in mammalian host cells and whether silencing suppressors can be encoded by mammalian viruses. We also review the modes of action proposed for some silencing suppressors.

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Identification of a Conserved Motif That Is Necessary for Binding of the Vaccinia Virus E3L Gene Products to Double-Stranded RNA

Cited by 149 publications

References 0 publications

Domain Structure of Human Nuclear DNA Helicase II (RNA Helicase A)

Domain Structure of Human Nuclear DNA Helicase II (RNA Helicase A)

A PKR-like eukaryotic initiation factor 2α kinase from zebrafish contains Z-DNA binding domains instead of dsRNA binding domains

Silencing suppressors: viral weapons for countering host cell defenses

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