Crystal structure of the unique RNA-binding domain of the influenza virus NS1 protein

1997 ◽  
Vol 4 (11) ◽  
pp. 896-899 ◽  
Author(s):  
Jinsong Liu ◽  
Patricia A. Lynch ◽  
Chen-ya Chien ◽  
Gaetano T. Montelione ◽  
Robert M. Krug ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Influenza Virus ◽  
Rna Binding ◽  
Binding Domain ◽  
Ns1 Protein ◽  
Rna Binding Domain

Crystal structure of the RNA-binding domain of the U1 small nuclear ribonucleoprotein A

Nature ◽  
1990 ◽  
Vol 348 (6301) ◽  
pp. 515-520 ◽  
Author(s):  
Kiyoshi Nagai ◽  
Chris Oubridge ◽  
Timm H. Jessen ◽  
Jade Li ◽  
Philip R. Evans
Keyword(s):  
Crystal Structure ◽  
Rna Binding ◽  
Binding Domain ◽  
Small Nuclear Ribonucleoprotein ◽  
Rna Binding Domain ◽  
Nuclear Ribonucleoprotein

scholarly journals The RNA- and TRIM25-Binding Domains of Influenza Virus NS1 Protein Are Essential for Suppression of NLRP3 Inflammasome-Mediated Interleukin-1β Secretion

2016 ◽  
Vol 90 (8) ◽  
pp. 4105-4114 ◽  
Author(s):  
Miyu Moriyama ◽  
I-Yin Chen ◽  
Atsushi Kawaguchi ◽  
Takumi Koshiba ◽  
Kyosuke Nagata ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Nlrp3 Inflammasome ◽  
Influenza A ◽  
Rna Binding ◽  
Nonstructural Protein ◽  
Binding Domain ◽  
Interleukin 1Β ◽  
Ns1 Protein ◽  
Caspase 1 ◽  
Nonstructural Protein 1

ABSTRACTInflammasomes are cytosolic multimolecular protein complexes that stimulate the activation of caspase-1 and the release of mature forms of interleukin-1β (IL-1β) and IL-18. We previously demonstrated that the influenza A virus M2 protein stimulates IL-1β secretion following activation of the nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome. The nonstructural protein 1 (NS1) of influenza virus inhibits caspase-1 activation and IL-1β secretion. However, the precise mechanism by which NS1 inhibits IL-1β secretion remains unknown. Here, we showed that J774A.1 macrophages stably expressing the NS1 protein inhibited IL-1β secretion after infection with recombinant influenza virus lacking the NS1 gene. Coimmunoprecipitation assay revealed that the NS1 protein interacts with NLRP3. Importantly, the NS1 protein inhibited the NLRP3/ASC-induced single-speck formation required for full activation of inflammasomes. The NS1 protein of other influenza virus strains, including a recent pandemic strain, also inhibited inflammasome-mediated IL-1β secretion. The NS1 RNA-binding domain (basic residues 38 and 41) and TRIM25-binding domain (acidic residues 96 and 97) were required for suppression of NLRP3 inflammasome-mediated IL-1β secretion. These results shed light on a mechanism by which the NS1 protein of influenza virus suppresses NLRP3 inflammasome-mediated IL-1β secretion.IMPORTANCEInnate immune sensing of influenza virus via pattern recognition receptors not only plays a key role in generating type I interferons but also triggers inflammatory responses. We previously demonstrated that the influenza A virus M2 protein activates the NLRP3 inflammasome, leading to the secretion of interleukin-1β (IL-1β) and IL-18 following the activation of caspase-1. Although the nonstructural protein 1 (NS1) of influenza virus inhibits IL-1β secretion, the precise mechanism by which it achieves this remains to be defined. Here, we demonstrate that the NS1 protein interacts with NLRP3 to suppress NLRP3 inflammasome activation. J774A.1 macrophages stably expressing the NS1 protein suppressed NLRP3-mediated IL-1β secretion. The NS1 RNA-binding domain (basic residues 38 and 41) and TRIM25-binding domain (acidic residues 96 and 97) are important for suppression of NLRP3 inflammasome-mediated IL-1β secretion. These results will facilitate the development of new anti-inflammatory drugs.

scholarly journals Crystal structure of SARS-CoV-2 nucleocapsid protein RNA binding domain reveals potential unique drug targeting sites

2020 ◽  
Author(s):  
Sisi Kang ◽  
Mei Yang ◽  
Zhongsi Hong ◽  
Liping Zhang ◽  
Zhaoxia Huang ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Nucleocapsid Protein ◽  
Rna Binding ◽  
Structural Information ◽  
Antiviral Drug ◽  
Binding Domain ◽  
Binding Studies ◽  
Terminal Domain ◽  
Rna Binding Domain

AbstractThe outbreak of coronavirus disease (COVID-19) in China caused by SARS-CoV-2 virus continually lead to worldwide human infections and deaths. It is currently no specific viral protein targeted therapeutics yet. Viral nucleocapsid protein is a potential antiviral drug target, serving multiple critical functions during the viral life cycle. However, the structural information of SARS-CoV-2 nucleocapsid protein is yet to be clear. Herein, we have determined the 2.7 Å crystal structure of the N-terminal RNA binding domain of SARS-CoV-2 nucleocapsid protein. Although overall structure is similar with other reported coronavirus nucleocapsid protein N-terminal domain, the surface electrostatic potential characteristics between them are distinct. Further comparison with mild virus type HCoV-OC43 equivalent domain demonstrates a unique potential RNA binding pocket alongside the β-sheet core. Complemented by in vitro binding studies, our data provide several atomic resolution features of SARS-CoV-2 nucleocapsid protein N-terminal domain, guiding the design of novel antiviral agents specific targeting to SARS-CoV-2.

Crystal structure of the RNA-binding domain from transcription termination factor rho

1998 ◽  
Vol 5 (5) ◽  
pp. 352-356 ◽  
Author(s):  
Timothy J. Allison ◽  
Todd C. Wood ◽  
Deborah M. Briercheck ◽  
Fraydoon Rastinejad ◽  
John P. Richardson ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Rna Binding ◽  
Transcription Termination ◽  
Binding Domain ◽  
Termination Factor ◽  
Transcription Termination Factor ◽  
Rna Binding Domain

Molecular dissection of influenza virus nucleoprotein: deletion mapping of the RNA binding domain.

1994 ◽  
Vol 68 (12) ◽  
pp. 8433-8436 ◽  
Author(s):  
M Kobayashi ◽  
T Toyoda ◽  
D M Adyshev ◽  
Y Azuma ◽  
A Ishihama
Keyword(s):  
Influenza Virus ◽  
Rna Binding ◽  
Binding Domain ◽  
Deletion Mapping ◽  
Molecular Dissection ◽  
Rna Binding Domain

scholarly journals Eukaryotic Translation Initiation Factor 4GI Is a Cellular Target for NS1 Protein, a Translational Activator of Influenza Virus

2000 ◽  
Vol 20 (17) ◽  
pp. 6259-6268 ◽  
Author(s):  
Tomás Aragón ◽  
Susana de la Luna ◽  
Isabel Novoa ◽  
Luis Carrasco ◽  
Juan Ortín ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Rna Binding ◽  
Binding Domain ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Virus Protein ◽  
Published Data ◽  
Ns1 Protein ◽  
Cellular Mrnas

ABSTRACT Influenza virus NS1 protein is an RNA-binding protein whose expression alters several posttranscriptional regulatory processes, like polyadenylation, splicing, and nucleocytoplasmic transport of cellular mRNAs. In addition, NS1 protein enhances the translational rate of viral, but not cellular, mRNAs. To characterize this effect, we looked for targets of NS1 influenza virus protein among cellular translation factors. We found that NS1 coimmunoprecipitates with eukaryotic initiation factor 4GI (eIF4GI), the large subunit of the cap-binding complex eIF4F, either in influenza virus-infected cells or in cells transfected with NS1 cDNA. Affinity chromatography studies using a purified His-NS1 protein-containing matrix showed that the fusion protein pulls down endogenous eIF4GI from COS-1 cells and labeled eIF4GI translated in vitro, but not the eIF4E subunit of the eIF4F factor. Similar in vitro binding experiments with eIF4GI deletion mutants indicated that the NS1-binding domain of eIF4GI is located between residues 157 and 550, in a region where no other component of the translational machinery is known to interact. Moreover, using overlay assays and pull-down experiments, we showed that NS1 and eIF4GI proteins interact directly, in an RNA-independent manner. Mapping of the eIF4GI-binding domain in the NS1 protein indicated that the first 113 N-terminal amino acids of the protein, but not the first 81, are sufficient to bind eIF4GI. The first of these mutants has been previously shown to act as a translational enhancer, while the second is defective in this activity. Collectively, these and previously published data suggest a model where NS1 recruits eIF4GI specifically to the 5′ untranslated region (5′ UTR) of the viral mRNA, allowing for the preferential translation of the influenza virus messengers.

Crystal structure at 1.92 Å resolution of the RNA-binding domain of the U1A spliceosomal protein complexed with an RNA hairpin

Nature ◽  
1994 ◽  
Vol 372 (6505) ◽  
pp. 432-438 ◽  
Author(s):  
Chris Oubridge ◽  
Nobutoshi Ito ◽  
Philip R. Evans ◽  
C.-Hiang Teo ◽  
Kiyoshi Nagai
Keyword(s):  
Crystal Structure ◽  
Rna Binding ◽  
Binding Domain ◽  
Spliceosomal Protein ◽  
Rna Binding Domain ◽  
Rna Hairpin
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