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| | <StructureSection load='1xeq' size='340' side='right'caption='[[1xeq]], [[Resolution|resolution]] 2.10Å' scene=''> | | <StructureSection load='1xeq' size='340' side='right'caption='[[1xeq]], [[Resolution|resolution]] 2.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1xeq]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XEQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1XEQ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1xeq]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Influenza_B_virus_(B/Lee/1940) Influenza B virus (B/Lee/1940)]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XEQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1XEQ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BR:BROMIDE+ION'>BR</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1ns1|1ns1]]</div></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BR:BROMIDE+ION'>BR</scene></td></tr> |
| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1xeq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xeq OCA], [https://pdbe.org/1xeq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1xeq RCSB], [https://www.ebi.ac.uk/pdbsum/1xeq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1xeq ProSAT], [https://www.topsan.org/Proteins/NESGC/1xeq TOPSAN]</span></td></tr> | | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1xeq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xeq OCA], [https://pdbe.org/1xeq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1xeq RCSB], [https://www.ebi.ac.uk/pdbsum/1xeq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1xeq ProSAT], [https://www.topsan.org/Proteins/NESGC/1xeq TOPSAN]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/NS1_INBLE NS1_INBLE]] Binds and inhibits the ubiquitin-like protein G1P2/ISG15, which is an early antiviral protein. Inhibits IRF-3 nuclear translocation and activation. Inhibits IFN-beta promoter activation; this inhibition is not dsRNA-binding dependent Prevents EIF2AK2/PKR activation, either by binding double strand RNA or by interacting directly with EIF2AK2/PKR. Also binds poly(A) and U6 snRNA. Suppresses the RNA silencing-based antiviral response in Drosophila cells.<ref>PMID:15479798</ref>
| + | [https://www.uniprot.org/uniprot/NS1_INBLE NS1_INBLE] Binds and inhibits the ubiquitin-like protein G1P2/ISG15, which is an early antiviral protein. Inhibits IRF-3 nuclear translocation and activation. Inhibits IFN-beta promoter activation; this inhibition is not dsRNA-binding dependent Prevents EIF2AK2/PKR activation, either by binding double strand RNA or by interacting directly with EIF2AK2/PKR. Also binds poly(A) and U6 snRNA. Suppresses the RNA silencing-based antiviral response in Drosophila cells.<ref>PMID:15479798</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Khan, J A]] | + | [[Category: Khan JA]] |
| - | [[Category: Krug, R M]] | + | [[Category: Krug RM]] |
| - | [[Category: Montelione, G T]] | + | [[Category: Montelione GT]] |
| - | [[Category: Structural genomic]]
| + | [[Category: Tong L]] |
| - | [[Category: Tong, L]] | + | [[Category: Yin C]] |
| - | [[Category: Yin, C]] | + | |
| - | [[Category: Influenza b virus]]
| + | |
| - | [[Category: Nesg]]
| + | |
| - | [[Category: Non-structural protein]]
| + | |
| - | [[Category: Ns1b]]
| + | |
| - | [[Category: PSI, Protein structure initiative]]
| + | |
| - | [[Category: Rna binding domain]]
| + | |
| - | [[Category: Viral protein]]
| + | |
| Structural highlights
Function
NS1_INBLE Binds and inhibits the ubiquitin-like protein G1P2/ISG15, which is an early antiviral protein. Inhibits IRF-3 nuclear translocation and activation. Inhibits IFN-beta promoter activation; this inhibition is not dsRNA-binding dependent Prevents EIF2AK2/PKR activation, either by binding double strand RNA or by interacting directly with EIF2AK2/PKR. Also binds poly(A) and U6 snRNA. Suppresses the RNA silencing-based antiviral response in Drosophila cells.[1]
Publication Abstract from PubMed
Influenza A viruses cause a highly contagious respiratory disease in humans and are responsible for periodic widespread epidemics with high mortality rates. The influenza A virus NS1 protein (NS1A) plays a key role in countering host antiviral defense and in virulence. The 73-residue N-terminal domain of NS1A (NS1A-(1-73)) forms a symmetric homodimer with a unique six-helical chain fold. It binds canonical A-form double-stranded RNA (dsRNA). Mutational inactivation of this dsRNA binding activity of NS1A highly attenuates virus replication. Here, we have characterized the unique structural features of the dsRNA binding surface of NS1A-(1-73) using NMR methods and describe the 2.1-A x-ray crystal structure of the corresponding dsRNA binding domain from human influenza B virus NS1B-(15-93). These results identify conserved dsRNA binding surfaces on both NS1A-(1-73) and NS1B-(15-93) that are very different from those indicated in earlier "working models" of the complex between dsRNA and NS1A-(1-73). The combined NMR and crystallographic data reveal highly conserved surface tracks of basic and hydrophilic residues that interact with dsRNA. These tracks are structurally complementary to the polyphosphate backbone conformation of A-form dsRNA and run at an approximately 45 degrees angle relative to the axes of helices alpha2/alpha2'. At the center of this dsRNA binding epitope, and common to NS1 proteins from influenza A and B viruses, is a deep pocket that includes both hydrophilic and hydrophobic amino acids. This pocket provides a target on the surface of the NS1 protein that is potentially suitable for the development of antiviral drugs targeting both influenza A and B viruses.
Conserved surface features form the double-stranded RNA binding site of non-structural protein 1 (NS1) from influenza A and B viruses.,Yin C, Khan JA, Swapna GV, Ertekin A, Krug RM, Tong L, Montelione GT J Biol Chem. 2007 Jul 13;282(28):20584-92. Epub 2007 May 1. PMID:17475623[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Donelan NR, Dauber B, Wang X, Basler CF, Wolff T, Garcia-Sastre A. The N- and C-terminal domains of the NS1 protein of influenza B virus can independently inhibit IRF-3 and beta interferon promoter activation. J Virol. 2004 Nov;78(21):11574-82. PMID:15479798 doi:78/21/11574
- ↑ Yin C, Khan JA, Swapna GV, Ertekin A, Krug RM, Tong L, Montelione GT. Conserved surface features form the double-stranded RNA binding site of non-structural protein 1 (NS1) from influenza A and B viruses. J Biol Chem. 2007 Jul 13;282(28):20584-92. Epub 2007 May 1. PMID:17475623 doi:10.1074/jbc.M611619200
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