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http://purl.uniprot.org/citations/23319625http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/23319625http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/23319625http://www.w3.org/2000/01/rdf-schema#comment"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 Å 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."xsd:string
http://purl.uniprot.org/citations/23319625http://purl.org/dc/terms/identifier"doi:10.1073/pnas.1218528110"xsd:string
http://purl.uniprot.org/citations/23319625http://purl.org/dc/terms/identifier"doi:10.1073/pnas.1218528110"xsd:string
http://purl.uniprot.org/citations/23319625http://purl.uniprot.org/core/author"Dufner M."xsd:string
http://purl.uniprot.org/citations/23319625http://purl.uniprot.org/core/author"Dufner M."xsd:string
http://purl.uniprot.org/citations/23319625http://purl.uniprot.org/core/author"Donovan J."xsd:string
http://purl.uniprot.org/citations/23319625http://purl.uniprot.org/core/author"Donovan J."xsd:string
http://purl.uniprot.org/citations/23319625http://purl.uniprot.org/core/author"Korennykh A."xsd:string
http://purl.uniprot.org/citations/23319625http://purl.uniprot.org/core/author"Korennykh A."xsd:string
http://purl.uniprot.org/citations/23319625http://purl.uniprot.org/core/date"2013"xsd:gYear
http://purl.uniprot.org/citations/23319625http://purl.uniprot.org/core/date"2013"xsd:gYear
http://purl.uniprot.org/citations/23319625http://purl.uniprot.org/core/name"Proc. Natl. Acad. Sci. U.S.A."xsd:string
http://purl.uniprot.org/citations/23319625http://purl.uniprot.org/core/name"Proc. Natl. Acad. Sci. U.S.A."xsd:string
http://purl.uniprot.org/citations/23319625http://purl.uniprot.org/core/pages"1652-1657"xsd:string
http://purl.uniprot.org/citations/23319625http://purl.uniprot.org/core/pages"1652-1657"xsd:string
http://purl.uniprot.org/citations/23319625http://purl.uniprot.org/core/title"Structural basis for cytosolic double-stranded RNA surveillance by human oligoadenylate synthetase 1."xsd:string
http://purl.uniprot.org/citations/23319625http://purl.uniprot.org/core/title"Structural basis for cytosolic double-stranded RNA surveillance by human oligoadenylate synthetase 1."xsd:string
http://purl.uniprot.org/citations/23319625http://purl.uniprot.org/core/volume"110"xsd:string
http://purl.uniprot.org/citations/23319625http://purl.uniprot.org/core/volume"110"xsd:string
http://purl.uniprot.org/citations/23319625http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/23319625
http://purl.uniprot.org/citations/23319625http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/23319625
http://purl.uniprot.org/citations/23319625http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/23319625
http://purl.uniprot.org/citations/23319625http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/23319625