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| | ==Crystal structure of human ISG15 in complex with NS1 N-terminal region from influenza virus B, Northeast Structural Genomics Consortium Target IDs HX6481, HR2873, and OR2== | | ==Crystal structure of human ISG15 in complex with NS1 N-terminal region from influenza virus B, Northeast Structural Genomics Consortium Target IDs HX6481, HR2873, and OR2== |
| - | <StructureSection load='3r66' size='340' side='right' caption='[[3r66]], [[Resolution|resolution]] 2.30Å' scene=''> | + | <StructureSection load='3r66' size='340' side='right'caption='[[3r66]], [[Resolution|resolution]] 2.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3r66]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/ ] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3R66 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3R66 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3r66]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/ ] and [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3R66 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3R66 FirstGlance]. <br> |
| | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSD:3-SULFINOALANINE'>CSD</scene></td></tr> | | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSD:3-SULFINOALANINE'>CSD</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1xeq|1xeq]], [[1z2m|1z2m]]</td></tr> | + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1xeq|1xeq]], [[1z2m|1z2m]]</div></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ISG15, G1P2, UCRP ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ISG15, G1P2, UCRP ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=3r66 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3r66 OCA], [http://pdbe.org/3r66 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3r66 RCSB], [http://www.ebi.ac.uk/pdbsum/3r66 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3r66 ProSAT]</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=3r66 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3r66 OCA], [https://pdbe.org/3r66 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3r66 RCSB], [https://www.ebi.ac.uk/pdbsum/3r66 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3r66 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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> [[http://www.uniprot.org/uniprot/ISG15_HUMAN ISG15_HUMAN]] Ubiquitin-like protein that is conjugated to intracellular target proteins after IFN-alpha or IFN-beta stimulation. Its enzymatic pathway is partially distinct from that of ubiquitin, differing in substrate specificity and interaction with ligating enzymes. ISG15 conjugation pathway uses a dedicated E1 enzyme, but seems to converge with the Ub conjugation pathway at the level of a specific E2 enzyme. Targets include STAT1, SERPINA3G/SPI2A, JAK1, MAPK3/ERK1, PLCG1, EIF2AK2/PKR, MX1/MxA, and RIG-1. Deconjugated by USP18/UBP43. Shows specific chemotactic activity towards neutrophils and activates them to induce release of eosinophil chemotactic factors. May serve as a trans-acting binding factor directing the association of ligated target proteins to intermediate filaments. May also be involved in autocrine, paracrine and endocrine mechanisms, as in cell-to-cell signaling, possibly partly by inducing IFN-gamma secretion by monocytes and macrophages. Seems to display antiviral activity during viral infections.<ref>PMID:1373138</ref> <ref>PMID:7526157</ref> <ref>PMID:8550581</ref> <ref>PMID:2005397</ref> <ref>PMID:16254333</ref> <ref>PMID:16009940</ref> In response to IFN-tau secreted by the conceptus, may ligate to and regulate proteins involved in the release of prostaglandin F2-alpha (PGF), and thus prevent lysis of the corpus luteum and maintain the pregnancy (By similarity).<ref>PMID:1373138</ref> <ref>PMID:7526157</ref> <ref>PMID:8550581</ref> <ref>PMID:2005397</ref> <ref>PMID:16254333</ref> <ref>PMID:16009940</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> [[https://www.uniprot.org/uniprot/ISG15_HUMAN ISG15_HUMAN]] Ubiquitin-like protein that is conjugated to intracellular target proteins after IFN-alpha or IFN-beta stimulation. Its enzymatic pathway is partially distinct from that of ubiquitin, differing in substrate specificity and interaction with ligating enzymes. ISG15 conjugation pathway uses a dedicated E1 enzyme, but seems to converge with the Ub conjugation pathway at the level of a specific E2 enzyme. Targets include STAT1, SERPINA3G/SPI2A, JAK1, MAPK3/ERK1, PLCG1, EIF2AK2/PKR, MX1/MxA, and RIG-1. Deconjugated by USP18/UBP43. Shows specific chemotactic activity towards neutrophils and activates them to induce release of eosinophil chemotactic factors. May serve as a trans-acting binding factor directing the association of ligated target proteins to intermediate filaments. May also be involved in autocrine, paracrine and endocrine mechanisms, as in cell-to-cell signaling, possibly partly by inducing IFN-gamma secretion by monocytes and macrophages. Seems to display antiviral activity during viral infections.<ref>PMID:1373138</ref> <ref>PMID:7526157</ref> <ref>PMID:8550581</ref> <ref>PMID:2005397</ref> <ref>PMID:16254333</ref> <ref>PMID:16009940</ref> In response to IFN-tau secreted by the conceptus, may ligate to and regulate proteins involved in the release of prostaglandin F2-alpha (PGF), and thus prevent lysis of the corpus luteum and maintain the pregnancy (By similarity).<ref>PMID:1373138</ref> <ref>PMID:7526157</ref> <ref>PMID:8550581</ref> <ref>PMID:2005397</ref> <ref>PMID:16254333</ref> <ref>PMID:16009940</ref> |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Human]] | | [[Category: Human]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Guan, R]] | | [[Category: Guan, R]] |
| | [[Category: Krug, R M]] | | [[Category: Krug, R M]] |
| 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] [ISG15_HUMAN] Ubiquitin-like protein that is conjugated to intracellular target proteins after IFN-alpha or IFN-beta stimulation. Its enzymatic pathway is partially distinct from that of ubiquitin, differing in substrate specificity and interaction with ligating enzymes. ISG15 conjugation pathway uses a dedicated E1 enzyme, but seems to converge with the Ub conjugation pathway at the level of a specific E2 enzyme. Targets include STAT1, SERPINA3G/SPI2A, JAK1, MAPK3/ERK1, PLCG1, EIF2AK2/PKR, MX1/MxA, and RIG-1. Deconjugated by USP18/UBP43. Shows specific chemotactic activity towards neutrophils and activates them to induce release of eosinophil chemotactic factors. May serve as a trans-acting binding factor directing the association of ligated target proteins to intermediate filaments. May also be involved in autocrine, paracrine and endocrine mechanisms, as in cell-to-cell signaling, possibly partly by inducing IFN-gamma secretion by monocytes and macrophages. Seems to display antiviral activity during viral infections.[2] [3] [4] [5] [6] [7] In response to IFN-tau secreted by the conceptus, may ligate to and regulate proteins involved in the release of prostaglandin F2-alpha (PGF), and thus prevent lysis of the corpus luteum and maintain the pregnancy (By similarity).[8] [9] [10] [11] [12] [13]
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
- ↑ Loeb KR, Haas AL. The interferon-inducible 15-kDa ubiquitin homolog conjugates to intracellular proteins. J Biol Chem. 1992 Apr 15;267(11):7806-13. PMID:1373138
- ↑ Loeb KR, Haas AL. Conjugates of ubiquitin cross-reactive protein distribute in a cytoskeletal pattern. Mol Cell Biol. 1994 Dec;14(12):8408-19. PMID:7526157
- ↑ Narasimhan J, Potter JL, Haas AL. Conjugation of the 15-kDa interferon-induced ubiquitin homolog is distinct from that of ubiquitin. J Biol Chem. 1996 Jan 5;271(1):324-30. PMID:8550581
- ↑ Knight E Jr, Cordova B. IFN-induced 15-kDa protein is released from human lymphocytes and monocytes. J Immunol. 1991 Apr 1;146(7):2280-4. PMID:2005397
- ↑ Lenschow DJ, Giannakopoulos NV, Gunn LJ, Johnston C, O'Guin AK, Schmidt RE, Levine B, Virgin HW 4th. Identification of interferon-stimulated gene 15 as an antiviral molecule during Sindbis virus infection in vivo. J Virol. 2005 Nov;79(22):13974-83. PMID:16254333 doi:79/22/13974
- ↑ Zhao C, Denison C, Huibregtse JM, Gygi S, Krug RM. Human ISG15 conjugation targets both IFN-induced and constitutively expressed proteins functioning in diverse cellular pathways. Proc Natl Acad Sci U S A. 2005 Jul 19;102(29):10200-5. Epub 2005 Jul 11. PMID:16009940 doi:0504754102
- ↑ Loeb KR, Haas AL. The interferon-inducible 15-kDa ubiquitin homolog conjugates to intracellular proteins. J Biol Chem. 1992 Apr 15;267(11):7806-13. PMID:1373138
- ↑ Loeb KR, Haas AL. Conjugates of ubiquitin cross-reactive protein distribute in a cytoskeletal pattern. Mol Cell Biol. 1994 Dec;14(12):8408-19. PMID:7526157
- ↑ Narasimhan J, Potter JL, Haas AL. Conjugation of the 15-kDa interferon-induced ubiquitin homolog is distinct from that of ubiquitin. J Biol Chem. 1996 Jan 5;271(1):324-30. PMID:8550581
- ↑ Knight E Jr, Cordova B. IFN-induced 15-kDa protein is released from human lymphocytes and monocytes. J Immunol. 1991 Apr 1;146(7):2280-4. PMID:2005397
- ↑ Lenschow DJ, Giannakopoulos NV, Gunn LJ, Johnston C, O'Guin AK, Schmidt RE, Levine B, Virgin HW 4th. Identification of interferon-stimulated gene 15 as an antiviral molecule during Sindbis virus infection in vivo. J Virol. 2005 Nov;79(22):13974-83. PMID:16254333 doi:79/22/13974
- ↑ Zhao C, Denison C, Huibregtse JM, Gygi S, Krug RM. Human ISG15 conjugation targets both IFN-induced and constitutively expressed proteins functioning in diverse cellular pathways. Proc Natl Acad Sci U S A. 2005 Jul 19;102(29):10200-5. Epub 2005 Jul 11. PMID:16009940 doi:0504754102
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