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| | ==Structural basis for cytosolic double-stranded RNA surveillance by human OAS1== | | ==Structural basis for cytosolic double-stranded RNA surveillance by human OAS1== |
| - | <StructureSection load='4ig8' size='340' side='right' caption='[[4ig8]], [[Resolution|resolution]] 2.70Å' scene=''> | + | <StructureSection load='4ig8' size='340' side='right'caption='[[4ig8]], [[Resolution|resolution]] 2.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4ig8]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IG8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4IG8 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4ig8]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IG8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4IG8 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DTP:2-DEOXYADENOSINE+5-TRIPHOSPHATE'>DTP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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]] 2.7Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">OAS1, OIAS ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DTP:2-DEOXYADENOSINE+5-TRIPHOSPHATE'>DTP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></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=4ig8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ig8 OCA], [http://pdbe.org/4ig8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ig8 RCSB], [http://www.ebi.ac.uk/pdbsum/4ig8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ig8 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=4ig8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ig8 OCA], [https://pdbe.org/4ig8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ig8 RCSB], [https://www.ebi.ac.uk/pdbsum/4ig8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ig8 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/OAS1_HUMAN OAS1_HUMAN]] Interferon-induced, dsRNA-activated antiviral enzyme which plays a critical role in cellular innate antiviral response. In addition, it may also play a role in other cellular processes such as apoptosis, cell growth, differentiation and gene regulation. Synthesizes higher oligomers of 2'-5'-oligoadenylates (2-5A) from ATP which then bind to the inactive monomeric form of ribonuclease L (RNase L) leading to its dimerization and subsequent activation. Activation of RNase L leads to degradation of cellular as well as viral RNA, resulting in the inhibition of protein synthesis, thus terminating viral replication. Can mediate the antiviral effect via the classical RNase L-dependent pathway or an alternative antiviral pathway independent of RNase L. The secreted form displays antiviral effect against vesicular stomatitis virus (VSV), herpes simplex virus type 2 (HSV-2), and encephalomyocarditis virus (EMCV) and stimulates the alternative antiviral pathway independent of RNase L.<ref>PMID:12799444</ref> <ref>PMID:18931074</ref> <ref>PMID:19923450</ref> <ref>PMID:23319625</ref> | + | [https://www.uniprot.org/uniprot/OAS1_HUMAN OAS1_HUMAN] Interferon-induced, dsRNA-activated antiviral enzyme which plays a critical role in cellular innate antiviral response. In addition, it may also play a role in other cellular processes such as apoptosis, cell growth, differentiation and gene regulation. Synthesizes higher oligomers of 2'-5'-oligoadenylates (2-5A) from ATP which then bind to the inactive monomeric form of ribonuclease L (RNase L) leading to its dimerization and subsequent activation. Activation of RNase L leads to degradation of cellular as well as viral RNA, resulting in the inhibition of protein synthesis, thus terminating viral replication. Can mediate the antiviral effect via the classical RNase L-dependent pathway or an alternative antiviral pathway independent of RNase L. The secreted form displays antiviral effect against vesicular stomatitis virus (VSV), herpes simplex virus type 2 (HSV-2), and encephalomyocarditis virus (EMCV) and stimulates the alternative antiviral pathway independent of RNase L.<ref>PMID:12799444</ref> <ref>PMID:18931074</ref> <ref>PMID:19923450</ref> <ref>PMID:23319625</ref> |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | The human sensor of double-stranded RNA (dsRNA) oligoadenylate synthetase 1 (hOAS1) polymerizes ATP into 2',5'-linked iso-RNA (2-5A) involved in innate immunity, cell cycle, and differentiation. We report the crystal structure of hOAS1 in complex with dsRNA and 2'-deoxy ATP at 2.7 A resolution, which reveals the mechanism of cytoplasmic dsRNA recognition and activation of oligoadenylate synthetases. Human OAS1 recognizes dsRNA using a previously uncharacterized protein/RNA interface that forms via a conformational change induced by binding of dsRNA. The protein/RNA interface involves two minor grooves and has no sequence-specific contacts, with the exception of a single hydrogen bond between the -NH(2) group of nucleobase G17 and the carbonyl oxygen of serine 56. Using a biochemical readout, we show that hOAS1 undergoes more than 20,000-fold activation upon dsRNA binding and that canonical or GU-wobble substitutions produce dsRNA mutants that retain either full or partial activity, in agreement with the crystal structure. Ultimately, the binding of dsRNA promotes an elaborate conformational rearrangement in the N-terminal lobe of hOAS1, which brings residues D75, D77, and D148 into proximity and creates coordination geometry for binding of two catalytic Mg(2+) ions and ATP. The assembly of this critical active-site structure provides the gate that couples binding of dsRNA to the production and downstream functions of 2-5A.
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| - | | + | |
| - | Structural basis for cytosolic double-stranded RNA surveillance by human oligoadenylate synthetase 1.,Donovan J, Dufner M, Korennykh A Proc Natl Acad Sci U S A. 2013 Jan 14. PMID:23319625<ref>PMID:23319625</ref>
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| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
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| - | <div class="pdbe-citations 4ig8" style="background-color:#fffaf0;"></div>
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| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Donovan, J]] | + | [[Category: Large Structures]] |
| - | [[Category: Korennykh, A]] | + | [[Category: Donovan J]] |
| - | [[Category: Cytosol]] | + | [[Category: Korennykh A]] |
| - | [[Category: Double-stranded rna]]
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| - | [[Category: Innate immune system double-stranded dsrna sensor rna polymerase]]
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| - | [[Category: Nucleotidyl transferase]]
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| - | [[Category: Nucleotidyl transferase 2-5a synthetase]]
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| - | [[Category: Rnase l activator]]
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| - | [[Category: Transferase-rna complex]]
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| Structural highlights
Function
OAS1_HUMAN Interferon-induced, dsRNA-activated antiviral enzyme which plays a critical role in cellular innate antiviral response. In addition, it may also play a role in other cellular processes such as apoptosis, cell growth, differentiation and gene regulation. Synthesizes higher oligomers of 2'-5'-oligoadenylates (2-5A) from ATP which then bind to the inactive monomeric form of ribonuclease L (RNase L) leading to its dimerization and subsequent activation. Activation of RNase L leads to degradation of cellular as well as viral RNA, resulting in the inhibition of protein synthesis, thus terminating viral replication. Can mediate the antiviral effect via the classical RNase L-dependent pathway or an alternative antiviral pathway independent of RNase L. The secreted form displays antiviral effect against vesicular stomatitis virus (VSV), herpes simplex virus type 2 (HSV-2), and encephalomyocarditis virus (EMCV) and stimulates the alternative antiviral pathway independent of RNase L.[1] [2] [3] [4]
References
- ↑ Eskildsen S, Justesen J, Schierup MH, Hartmann R. Characterization of the 2'-5'-oligoadenylate synthetase ubiquitin-like family. Nucleic Acids Res. 2003 Jun 15;31(12):3166-73. PMID:12799444
- ↑ Marques J, Anwar J, Eskildsen-Larsen S, Rebouillat D, Paludan SR, Sen G, Williams BR, Hartmann R. The p59 oligoadenylate synthetase-like protein possesses antiviral activity that requires the C-terminal ubiquitin-like domain. J Gen Virol. 2008 Nov;89(Pt 11):2767-72. doi: 10.1099/vir.0.2008/003558-0. PMID:18931074 doi:http://dx.doi.org/10.1099/vir.0.2008/003558-0
- ↑ Lin RJ, Yu HP, Chang BL, Tang WC, Liao CL, Lin YL. Distinct antiviral roles for human 2',5'-oligoadenylate synthetase family members against dengue virus infection. J Immunol. 2009 Dec 15;183(12):8035-43. doi: 10.4049/jimmunol.0902728. Epub . PMID:19923450 doi:http://dx.doi.org/10.4049/jimmunol.0902728
- ↑ Donovan J, Dufner M, Korennykh A. Structural basis for cytosolic double-stranded RNA surveillance by human oligoadenylate synthetase 1. Proc Natl Acad Sci U S A. 2013 Jan 14. PMID:23319625 doi:http://dx.doi.org/10.1073/pnas.1218528110
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