|
|
| (3 intermediate revisions not shown.) |
| Line 1: |
Line 1: |
| | + | |
| | ==Solution NMR structure of the monomeric W187R mutant of A/Udorn NS1 effector domain. Northeast Structural Genomics target OR8C[W187R].== | | ==Solution NMR structure of the monomeric W187R mutant of A/Udorn NS1 effector domain. Northeast Structural Genomics target OR8C[W187R].== |
| - | <StructureSection load='2kkz' size='340' side='right' caption='[[2kkz]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2kkz' size='340' side='right'caption='[[2kkz]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2kkz]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Influenza_a_virus Influenza a virus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KKZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2KKZ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2kkz]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Influenza_A_virus_(A/Hungary/2/1971(H3N2)) Influenza A virus (A/Hungary/2/1971(H3N2))]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KKZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2KKZ FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NS, NS1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11320 Influenza A virus])</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2kkz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kkz OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2kkz RCSB], [http://www.ebi.ac.uk/pdbsum/2kkz PDBsum], [http://www.topsan.org/Proteins/NESGC/2kkz 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=2kkz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kkz OCA], [https://pdbe.org/2kkz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2kkz RCSB], [https://www.ebi.ac.uk/pdbsum/2kkz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2kkz ProSAT], [https://www.topsan.org/Proteins/NESGC/2kkz TOPSAN]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/Q6XSU2_9INFA Q6XSU2_9INFA]] 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.[SAAS:SAAS00141143] 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.[SAAS:SAAS00141179] | + | [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> |
| | + | == References == |
| | + | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Influenza a virus]] | + | [[Category: Large Structures]] |
| - | [[Category: Aramini, J M]] | + | [[Category: Aramini JM]] |
| - | [[Category: Ciccosanti, C]] | + | [[Category: Ciccosanti C]] |
| - | [[Category: Cunningham, K]] | + | [[Category: Cunningham K]] |
| - | [[Category: Fang, Y]] | + | [[Category: Fang Y]] |
| - | [[Category: Janjua, H]] | + | [[Category: Janjua H]] |
| - | [[Category: Krug, R M]] | + | [[Category: Krug RM]] |
| - | [[Category: Lee, H]] | + | [[Category: Lee H]] |
| - | [[Category: Ma, L]] | + | [[Category: Ma L]] |
| - | [[Category: Montelione, G T]] | + | [[Category: Montelione GT]] |
| - | [[Category: Structural genomic]]
| + | [[Category: Xiao R]] |
| - | [[Category: Xiao, R]] | + | [[Category: Zhao L]] |
| - | [[Category: Zhao, L]] | + | |
| - | [[Category: Antiviral protein]]
| + | |
| - | [[Category: Effector domain]]
| + | |
| - | [[Category: Host-virus interaction]]
| + | |
| - | [[Category: Influenza some]]
| + | |
| - | [[Category: Interferon antiviral system evasion]]
| + | |
| - | [[Category: Nesg]]
| + | |
| - | [[Category: PSI, Protein structure initiative]]
| + | |
| - | [[Category: Solution nmr structure]]
| + | |
| - | [[Category: W187r mutant]]
| + | |
| 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]
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
|
