Recognition of the Rotavirus mRNA 3′ Consensus by an Asymmetric NSP3 Homodimer

Deo, Rahul C.; Groft, Caroline M.; Rajashankar, K.R.; Burley, S.K.

doi:10.1016/s0092-8674(01)00632-8

Cited by 93 publications

(75 citation statements)

References 39 publications

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“…To our knowledge, there is no precedent of such an asymmetric homodimer with distinct subunit structures, except for the N-terminal domain homodimer of nonstructural protein 3 (NSP3) from rotavirus (41). NSP3 binds to the viral mRNA and circularizes it for translation.…”

Section: Discussionmentioning

confidence: 99%

Insight into the flagella type III export revealed by the complex structure of the type III ATPase and its regulator

Imada

Minamino

Uchida

et al. 2016

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

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FliI and FliJ form the FliI 6 FliJ ATPase complex of the bacterial flagellar export apparatus, a member of the type III secretion system. The FliI 6 FliJ complex is structurally similar to the α 3 β 3 γ complex of F 1 -ATPase. The FliH homodimer binds to FliI to connect the ATPase complex to the flagellar base, but the details are unknown. Here we report the structure of the homodimer of a C-terminal fragment of FliH (FliH C2 ) in complex with FliI. FliH C2 shows an unusually asymmetric homodimeric structure that markedly resembles the peripheral stalk of the A/V-type ATPases. The FliH C2 -FliI hexamer model reveals that the C-terminal domains of the FliI ATPase face the cell membrane in a way similar to the F/A/V-type ATPases. We discuss the mechanism of flagellar ATPase complex formation and a common origin shared by the type III secretion system and the F/A/V-type ATPases.bacterial flagellum | type III protein export | crystal structure | F/A/V-type ATPase

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Section: Discussionmentioning

confidence: 99%

Insight into the flagella type III export revealed by the complex structure of the type III ATPase and its regulator

Imada

Minamino

Uchida

et al. 2016

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

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“…A colon shows a conserved amino acid between GBR and GAR, or GBR and GCR. The RNA-binding domain (Deo et al, 2002) is indicated by a line above the sequences. Shaded regions indicate a-helices (H1-H8) and b-strands (S1-S3) in the RNA-binding domain.…”

Section: Discussionmentioning

confidence: 99%

“…Among the NSP3 sequences of GBRs, the N-terminal 120 aa region was highly conserved and corresponded to the RNA-binding region revealed for GAR NSP3 (Deo et al, 2002) (Fig. 4).…”

Section: Full-genome Analysis Of Human Group B Rotavirusmentioning

confidence: 99%

Analysis of genetic diversity and molecular evolution of human group B rotaviruses based on whole genome segments

Yamamoto

Ghosh

Ganesh

et al. 2010

Journal of General Virology

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Group B rotavirus (GBR) is a rare enteric pathogen that causes severe diarrhoea, primarily in adults. Nearly full-length sequences of all 11 RNA segments were determined for human GBRs detected recently in India (IDH-084 in 2007, IC-008 in 2008, Bangladesh (Bang117 in 2003) and Myanmar (MMR-B1 in 2007), and analysed phylogenetically with the sequence data of GBRs reported previously. All RNA segments of GBR strains from India, Bangladesh and Myanmar showed .95 % nucleotide sequence identities. Among the 11 RNA segments, the VP6 and NSP2 genes showed the highest identities (.98 %), whilst the lowest identities were observed in the NSP4 gene (96.1 %), NSP5 gene (95.6 %) and VP8*-encoding region of the VP4 gene (95.9 %). Divergent or conserved regions in the deduced amino acid sequences of GBR VP1-VP4 and NSP1-NSP5 were similar to those in group A rotaviruses (GARs), and the functionally important motifs and structural characteristics in viral proteins known for GAR were conserved in all of the human GBRs. These findings suggest that, whilst the degree of genetic evolution may be dependent on each RNA segment, human GBR may have been evolving in a similar manner to GAR, associated with the similar functional roles of individual viral proteins. INTRODUCTIONRotavirus, a member of the family Reoviridae, is the most important viral pathogen causing gastroenteritis in humans. Rotavirus has 11 segments of double-stranded RNA (dsRNA) as a genome, and the virus particle is composed of three concentric layers, i.e. the outer capsid, inner capsid and core (Estes & Kapikian, 2007). The outer capsid consists of two structural proteins, VP4 and VP7, which are neutralization antigens. The inner capsid consists of structural protein VP6. Rotavirus is classified into five groups (A-E) and two putative groups (F and G), based on the antigenicity of the inner capsid protein VP6 and genomic characteristics (Kapikian et al., 2001). In humans, groups A, B and C have so far been detected. Group A rotavirus (GAR) is the most prevalent throughout the world and is recognized as the leading viral pathogen of acute gastroenteritis in children.Group B rotavirus (GBR) is genetically and antigenically distinct from GAR and has been detected in humans, mice, calves, pigs and sheep. In humans, GBR has been noted because it causes severe, cholera-like diarrhoea, mostly in adults (Mackow, 1995). GBR was first identified as adult diarrhoea rotavirus (ADRV) in nationwide outbreaks in China in 1982-1983 (Hung et al., 1983, 1984Wang et al., 1985), and the detection of this virus has been limited to China (Dai et al., 1987; Fang et al., 1989). They were subsequently detected in sporadic cases in India in 1997 and in Bangladesh in 2000, demonstrating the distribution of GBRs in Asian countries outside China (Krishnan et al., 1999;Sanekata et al., 2003). Thereafter, GBRs have again been detected in these countries in sporadic cases of diarrhoea (Barman et al., 2006;Rahman et al., 2007). The GenBank/EMBL/DDBJ accession numbers for the nucleotide sequen...

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“…The region of NSP3 that is necessary for its interaction with RoXaN I includes a portion of the NSP3 dimerization domain and is close to the eIF4G-binding domain (44). Dimerization of NSP3 is required for its eIF4G-and RNAbinding properties (13,22,44), and consequently, for its biological properties (61). By interacting with NSP3, RoXaN I could impair the binding of eIF4G to NSP3, either by disrupting NSP3 dimers or by concealing its eIF4G-binding site.…”

Section: Vol 78 2004mentioning

confidence: 99%

“…The amino-terminal domain (aa 1 to 150) is required for sequencespecific RNA binding (13,44). Our laboratory has shown that a dimer of NSP3 binds a single RNA molecule (44), and the three-dimensional structure of the amino terminus of NSP3 confirms this, showing a heart-shaped dimer bound to one RNA molecule (13). The central domain of NSP3 (aa 150 to 241) is predicted to form a coiled-coil structure, allowing NSP3 dimerization (44).…”

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confidence: 99%

RoXaN, a Novel Cellular Protein Containing TPR, LD, and Zinc Finger Motifs, Forms a Ternary Complex with Eukaryotic Initiation Factor 4G and Rotavirus NSP3

Vitour

Livet

Vende

et al. 2004

J Virol

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Rotavirus mRNAs are capped but not polyadenylated, and viral proteins are translated by the cellular translation machinery. This is accomplished through the action of the viral nonstructural protein NSP3, which specifically binds the 3 consensus sequence of viral mRNAs and interacts with the eukaryotic translation initiation factor eIF4G I. To further our understanding of the role of NSP3 in rotavirus replication, we looked for other cellular proteins capable of interacting with this viral protein. Using the yeast two-hybrid assay, we identified a novel cellular protein-binding partner for rotavirus NSP3. This 110-kDa cellular protein, named RoXaN (rotavirus X protein associated with NSP3), contains a minimum of three regions predicted to be involved in protein-protein or nucleic acid-protein interactions. A tetratricopeptide repeat region, a proteinprotein interaction domain most often found in multiprotein complexes, is present in the amino-terminal region. In the carboxy terminus, at least five zinc finger motifs are observed, further suggesting the capacity of RoXaN to bind other proteins or nucleic acids. Between these two regions exists a paxillin leucine-aspartate repeat (LD) motif which is involved in protein-protein interactions. RoXaN is capable of interacting with NSP3 in vivo and during rotavirus infection. Domains of interaction were mapped and correspond to the dimerization domain of NSP3 (amino acids 163 to 237) and the LD domain of RoXaN (amino acids 244 to 341). The interaction between NSP3 and RoXaN does not impair the interaction between NSP3 and eIF4G I, and a ternary complex made of NSP3, RoXaN, and eIF4G I can be detected in rotavirus-infected cells, implicating RoXaN in translation regulation.Rotaviruses, the major cause of diarrhea in young animals and children, are involved in the death of more than 400,000 children under the age of five each year (40, 41). Rotaviruses are members of the Reoviridae family, and their genomes are composed of 11 segments of double-stranded RNA which encode six structural proteins and five or six nonstructural proteins. The viral replication cycle occurs entirely in the cytoplasm. Upon virus entry, the viral transcriptase synthesizes capped, but nonpolyadenylated, mRNAs (16,28). These molecules are competent to serve as templates for either translation or replication. A subset of viral mRNAs are packaged into core particles and replicated to form the genomic doublestranded RNAs of progeny virions. Morphogenesis continues and viral proteins are added to generate the middle and outer layers surrounding the core particle. Mature virions, which consist of triple-layered particles, are released from the cell by lysis (reviewed in reference 16).Cellular translation involves a myriad of proteins and elements found at both the 5Ј and 3Ј termini of the majority of cellular mRNAs in a highly regulated cascade, controlled by specific protein-RNA and protein-protein interactions. In the steps leading to translational initiation, the cap structure at the 5Ј terminus of a...

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Recognition of the Rotavirus mRNA 3′ Consensus by an Asymmetric NSP3 Homodimer

Cited by 93 publications

References 39 publications

Insight into the flagella type III export revealed by the complex structure of the type III ATPase and its regulator

Insight into the flagella type III export revealed by the complex structure of the type III ATPase and its regulator

Analysis of genetic diversity and molecular evolution of human group B rotaviruses based on whole genome segments

RoXaN, a Novel Cellular Protein Containing TPR, LD, and Zinc Finger Motifs, Forms a Ternary Complex with Eukaryotic Initiation Factor 4G and Rotavirus NSP3

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