4ig8: Difference between revisions

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== Structural highlights ==
== Structural highlights ==
<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>
<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" id="ligandDat"><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]] 2.7&#8491;</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'>[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>
<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 ==
[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>  
[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.
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>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4ig8" style="background-color:#fffaf0;"></div>
== References ==
== References ==
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