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- | {{Seed}} | |
- | [[Image:1ail.png|left|200px]] | |
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- | <!--
| + | ==N-TERMINAL FRAGMENT OF NS1 PROTEIN FROM INFLUENZA A VIRUS== |
- | The line below this paragraph, containing "STRUCTURE_1ail", creates the "Structure Box" on the page.
| + | <StructureSection load='1ail' size='340' side='right'caption='[[1ail]], [[Resolution|resolution]] 1.90Å' scene=''> |
- | You may change the PDB parameter (which sets the PDB file loaded into the applet)
| + | == Structural highlights == |
- | or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
| + | <table><tr><td colspan='2'>[[1ail]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Influenza_A_virus_(A/Udorn/307/1972(H3N2)) Influenza A virus (A/Udorn/307/1972(H3N2))]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1AIL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1AIL FirstGlance]. <br> |
- | or leave the SCENE parameter empty for the default display. | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9Å</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=1ail FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ail OCA], [https://pdbe.org/1ail PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ail RCSB], [https://www.ebi.ac.uk/pdbsum/1ail PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ail ProSAT]</span></td></tr> |
- | {{STRUCTURE_1ail| PDB=1ail | SCENE= }}
| + | </table> |
| + | == Function == |
| + | [https://www.uniprot.org/uniprot/NS1_I72A2 NS1_I72A2] Inhibits post-transcriptional processing of cellular pre-mRNA, by binding and inhibiting two cellular proteins that are required for the 3'-end processing of cellular pre-mRNAs: the 30 kDa cleavage and polyadenylation specificity factor (CPSF4) and the poly(A)-binding protein 2 (PABPN1). This results in the accumulation of unprocessed 3' end pre-mRNAs which can't be exported from the nucleus. Cellular protein synthesis is thereby shut off very early after virus infection. Viral protein synthesis is not affected by the inhibition of the cellular 3' end processing machinery because the poly(A) tails of viral mRNAs are produced by the viral polymerase through a stuttering mechanism.<ref>PMID:9651582</ref> <ref>PMID:9560194</ref> <ref>PMID:16571812</ref> Prevents the establishment of the cellular antiviral state by inhibiting TRIM25-mediated DDX58 ubiquitination, which normally triggers the antiviral transduction signal that leads to the activation of type I IFN genes by transcription factors like IRF3 and IRF7. Prevents human EIF2AK2/PKR activation, either by binding double-strand RNA, or by interacting directly with EIF2AK2/PKR. This function may be important at the very beginning of the infection, when NS1 is mainly present in the cytoplasm. Also binds poly(A) and U6 snRNA. Suppresses the RNA silencing-based antiviral response in Drosophila cells (By similarity).<ref>PMID:9651582</ref> <ref>PMID:9560194</ref> <ref>PMID:16571812</ref> |
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- | ===N-TERMINAL FRAGMENT OF NS1 PROTEIN FROM INFLUENZA A VIRUS=== | + | ==See Also== |
- | | + | *[[Nonstructural protein 3D structures|Nonstructural protein 3D structures]] |
- | | + | == References == |
- | <!--
| + | <references/> |
- | The line below this paragraph, {{ABSTRACT_PUBMED_9360602}}, adds the Publication Abstract to the page
| + | __TOC__ |
- | (as it appears on PubMed at http://www.pubmed.gov), where 9360602 is the PubMed ID number.
| + | </StructureSection> |
- | -->
| + | [[Category: Large Structures]] |
- | {{ABSTRACT_PUBMED_9360602}}
| + | [[Category: Berman HM]] |
- | | + | [[Category: Chien C]] |
- | ==About this Structure==
| + | [[Category: Krug RM]] |
- | 1AIL is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Influenza_a_virus Influenza a virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1AIL OCA].
| + | [[Category: Liu J]] |
- | | + | [[Category: Lynch PA]] |
- | ==Reference== | + | [[Category: Montelione GT]] |
- | Crystal structure of the unique RNA-binding domain of the influenza virus NS1 protein., Liu J, Lynch PA, Chien CY, Montelione GT, Krug RM, Berman HM, Nat Struct Biol. 1997 Nov;4(11):896-9. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/9360602 9360602]
| + | |
- | [[Category: Influenza a virus]] | + | |
- | [[Category: Single protein]]
| + | |
- | [[Category: Berman, H M.]] | + | |
- | [[Category: Chien, C.]] | + | |
- | [[Category: Krug, R M.]] | + | |
- | [[Category: Liu, J.]] | + | |
- | [[Category: Lynch, P A.]] | + | |
- | [[Category: Montelione, G T.]] | + | |
- | [[Category: Nonstructural protein]]
| + | |
- | [[Category: Rna-binding protein]]
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- | | + | |
- | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jun 30 16:55:37 2008''
| + | |
| Structural highlights
Function
NS1_I72A2 Inhibits post-transcriptional processing of cellular pre-mRNA, by binding and inhibiting two cellular proteins that are required for the 3'-end processing of cellular pre-mRNAs: the 30 kDa cleavage and polyadenylation specificity factor (CPSF4) and the poly(A)-binding protein 2 (PABPN1). This results in the accumulation of unprocessed 3' end pre-mRNAs which can't be exported from the nucleus. Cellular protein synthesis is thereby shut off very early after virus infection. Viral protein synthesis is not affected by the inhibition of the cellular 3' end processing machinery because the poly(A) tails of viral mRNAs are produced by the viral polymerase through a stuttering mechanism.[1] [2] [3] Prevents the establishment of the cellular antiviral state by inhibiting TRIM25-mediated DDX58 ubiquitination, which normally triggers the antiviral transduction signal that leads to the activation of type I IFN genes by transcription factors like IRF3 and IRF7. Prevents human EIF2AK2/PKR activation, either by binding double-strand RNA, or by interacting directly with EIF2AK2/PKR. This function may be important at the very beginning of the infection, when NS1 is mainly present in the cytoplasm. Also binds poly(A) and U6 snRNA. Suppresses the RNA silencing-based antiviral response in Drosophila cells (By similarity).[4] [5] [6]
See Also
References
- ↑ Nemeroff ME, Barabino SM, Li Y, Keller W, Krug RM. Influenza virus NS1 protein interacts with the cellular 30 kDa subunit of CPSF and inhibits 3'end formation of cellular pre-mRNAs. Mol Cell. 1998 Jun;1(7):991-1000. PMID:9651582
- ↑ Li Y, Yamakita Y, Krug RM. Regulation of a nuclear export signal by an adjacent inhibitory sequence: the effector domain of the influenza virus NS1 protein. Proc Natl Acad Sci U S A. 1998 Apr 28;95(9):4864-9. PMID:9560194
- ↑ Twu KY, Noah DL, Rao P, Kuo RL, Krug RM. The CPSF30 binding site on the NS1A protein of influenza A virus is a potential antiviral target. J Virol. 2006 Apr;80(8):3957-65. PMID:16571812 doi:10.1128/JVI.80.8.3957-3965.2006
- ↑ Nemeroff ME, Barabino SM, Li Y, Keller W, Krug RM. Influenza virus NS1 protein interacts with the cellular 30 kDa subunit of CPSF and inhibits 3'end formation of cellular pre-mRNAs. Mol Cell. 1998 Jun;1(7):991-1000. PMID:9651582
- ↑ Li Y, Yamakita Y, Krug RM. Regulation of a nuclear export signal by an adjacent inhibitory sequence: the effector domain of the influenza virus NS1 protein. Proc Natl Acad Sci U S A. 1998 Apr 28;95(9):4864-9. PMID:9560194
- ↑ Twu KY, Noah DL, Rao P, Kuo RL, Krug RM. The CPSF30 binding site on the NS1A protein of influenza A virus is a potential antiviral target. J Virol. 2006 Apr;80(8):3957-65. PMID:16571812 doi:10.1128/JVI.80.8.3957-3965.2006
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