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4ig8

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Revision as of 07:12, 23 December 2016

Structural basis for cytosolic double-stranded RNA surveillance by human OAS1

Structural highlights

4ig8 is a 3 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Gene:	OAS1, OIAS (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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]

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^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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
↑ 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

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4ig8"

@@ Line 1: / Line 1: @@
 ==Structural basis for cytosolic double-stranded RNA surveillance by human OAS1==
 <StructureSection load='4ig8' size='340' side='right' caption='[[4ig8]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4ig8]] is a 3 chain structure with sequence from [http://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 [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 [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>
 </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>
-<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 Homo sapiens])</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='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://www.rcsb.org/pdb/explore.do?structureId=4ig8 RCSB], [http://www.ebi.ac.uk/pdbsum/4ig8 PDBsum]</span></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>
 </table>
+== 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>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 15: / Line 18: @@
 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/>
 __TOC__
 </StructureSection>
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Donovan, J]]
 [[Category: Korennykh, A]]

4ig8

From Proteopedia

Revision as of 07:12, 23 December 2016

Structural basis for cytosolic double-stranded RNA surveillance by human OAS1

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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