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| | ==The crystal structure of the OAS-like domain (OLD) of human OASL== | | ==The crystal structure of the OAS-like domain (OLD) of human OASL== |
| - | <StructureSection load='4xq7' size='340' side='right' caption='[[4xq7]], [[Resolution|resolution]] 1.60Å' scene=''> | + | <StructureSection load='4xq7' size='340' side='right'caption='[[4xq7]], [[Resolution|resolution]] 1.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4xq7]] is a 1 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=4XQ7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4XQ7 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4xq7]] is a 1 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=4XQ7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4XQ7 FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CME:S,S-(2-HYDROXYETHYL)THIOCYSTEINE'>CME</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]] 1.6Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">OASL, TRIP14 ([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=CME:S,S-(2-HYDROXYETHYL)THIOCYSTEINE'>CME</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=4xq7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xq7 OCA], [http://pdbe.org/4xq7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4xq7 RCSB], [http://www.ebi.ac.uk/pdbsum/4xq7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4xq7 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=4xq7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xq7 OCA], [https://pdbe.org/4xq7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4xq7 RCSB], [https://www.ebi.ac.uk/pdbsum/4xq7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4xq7 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/OASL_HUMAN OASL_HUMAN]] Does not have 2'-5'-OAS activity, but can bind double-stranded RNA. Displays antiviral activity against encephalomyocarditis virus (EMCV) and hepatitis C virus (HCV) via an alternative antiviral pathway independent of RNase L.<ref>PMID:9826176</ref> <ref>PMID:18931074</ref> <ref>PMID:20074559</ref> | + | [https://www.uniprot.org/uniprot/OASL_HUMAN OASL_HUMAN] Does not have 2'-5'-OAS activity, but can bind double-stranded RNA. Displays antiviral activity against encephalomyocarditis virus (EMCV) and hepatitis C virus (HCV) via an alternative antiviral pathway independent of RNase L.<ref>PMID:9826176</ref> <ref>PMID:18931074</ref> <ref>PMID:20074559</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Andersen, L L]] | + | [[Category: Large Structures]] |
| - | [[Category: Gad, H H]] | + | [[Category: Andersen LL]] |
| - | [[Category: Hartmann, R]] | + | [[Category: Gad HH]] |
| - | [[Category: Hornung, V]] | + | [[Category: Hartmann R]] |
| - | [[Category: Ibsen, M S]] | + | [[Category: Hornung V]] |
| - | [[Category: Julkunen, I]] | + | [[Category: Ibsen MS]] |
| - | [[Category: Sarkar, S N]] | + | [[Category: Julkunen I]] |
| - | [[Category: 2'-5' oligoadenylate synthetase]]
| + | [[Category: Sarkar SN]] |
| - | [[Category: Oa]]
| + | |
| - | [[Category: Oasl]]
| + | |
| - | [[Category: Oligoadenylate synthetase]]
| + | |
| - | [[Category: Oligoadenylate synthetase-like]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
OASL_HUMAN Does not have 2'-5'-OAS activity, but can bind double-stranded RNA. Displays antiviral activity against encephalomyocarditis virus (EMCV) and hepatitis C virus (HCV) via an alternative antiviral pathway independent of RNase L.[1] [2] [3]
Publication Abstract from PubMed
The oligoadenylate synthetase (OAS) enzymes are cytoplasmic dsRNA sensors belonging to the antiviral innate immune system. Upon binding to viral dsRNA, the OAS enzymes synthesize 2'-5' linked oligoadenylates (2-5As) that initiate an RNA decay pathway to impair viral replication. The human OAS-like (OASL) protein, however, does not harbor the catalytic activity required for synthesizing 2-5As and differs from the other human OAS family members by having two C-terminal ubiquitin-like domains. In spite of its lack of enzymatic activity, human OASL possesses antiviral activity. It was recently demonstrated that the ubiquitin-like domains of OASL could substitute for K63-linked poly-ubiquitin and interact with the CARDs of RIG-I and thereby enhance RIG-I signaling. However, the role of the OAS-like domain of OASL remains unclear. Here we present the crystal structure of the OAS-like domain, which shows a striking similarity with activated OAS1. Furthermore, the structure of the OAS-like domain shows that OASL has a dsRNA binding groove. We demonstrate that the OAS-like domain can bind dsRNA and that mutating key residues in the dsRNA binding site is detrimental to the RIG-I signaling enhancement. Hence, binding to dsRNA is an important feature of OASL that is required for enhancing RIG-I signaling.
Structural and functional analysis reveals that human OASL binds dsRNA to enhance RIG-I signaling.,Ibsen MS, Gad HH, Andersen LL, Hornung V, Julkunen I, Sarkar SN, Hartmann R Nucleic Acids Res. 2015 Apr 29. pii: gkv389. PMID:25925578[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Rebouillat D, Marie I, Hovanessian AG. Molecular cloning and characterization of two related and interferon-induced 56-kDa and 30-kDa proteins highly similar to 2'-5' oligoadenylate synthetase. Eur J Biochem. 1998 Oct 15;257(2):319-30. PMID:9826176
- ↑ 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
- ↑ Ishibashi M, Wakita T, Esumi M. 2',5'-Oligoadenylate synthetase-like gene highly induced by hepatitis C virus infection in human liver is inhibitory to viral replication in vitro. Biochem Biophys Res Commun. 2010 Feb 12;392(3):397-402. doi:, 10.1016/j.bbrc.2010.01.034. Epub 2010 Jan 13. PMID:20074559 doi:http://dx.doi.org/10.1016/j.bbrc.2010.01.034
- ↑ Ibsen MS, Gad HH, Andersen LL, Hornung V, Julkunen I, Sarkar SN, Hartmann R. Structural and functional analysis reveals that human OASL binds dsRNA to enhance RIG-I signaling. Nucleic Acids Res. 2015 Apr 29. pii: gkv389. PMID:25925578 doi:http://dx.doi.org/10.1093/nar/gkv389
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