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000279044 037__ $$aDZNE-2025-00674
000279044 041__ $$aEnglish
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000279044 1001_ $$aMerold, Veronika$$b0
000279044 245__ $$aStructural basis for OAS2 regulation and its antiviral function.
000279044 260__ $$a[Cambridge, Mass.]$$bCell Press$$c2025
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000279044 520__ $$aOligoadenylate synthetase (OAS) proteins are immune sensors for double-stranded RNA and are critical for restricting viruses. OAS2 comprises two OAS domains, only one of which can synthesize 2'-5'-oligoadenylates for RNase L activation. Existing structures of OAS1 provide a model for enzyme activation, but they do not explain how multiple OAS domains discriminate RNA length. Here, we discover that human OAS2 exists in an auto-inhibited state as a zinc-mediated dimer and present a mechanism for RNA length discrimination: the catalytically deficient domain acts as a molecular ruler that prevents autoreactivity to short RNAs. We demonstrate that dimerization and myristoylation localize OAS2 to Golgi membranes and that this is required for OAS2 activation and the restriction of viruses that exploit the endomembrane system for replication, e.g., coronaviruses. Finally, our results highlight the non-redundant role of OAS proteins and emphasize the clinical relevance of OAS2 by identifying a patient with a loss-of-function mutation associated with autoimmune disease.
000279044 536__ $$0G:(DE-HGF)POF4-351$$a351 - Brain Function (POF4-351)$$cPOF4-351$$fPOF IV$$x0
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000279044 650_7 $$2Other$$aOAS2
000279044 650_7 $$2Other$$aRNA sensing
000279044 650_7 $$2Other$$aRNase L
000279044 650_7 $$2Other$$ainnate immunity
000279044 650_7 $$2Other$$alocalization
000279044 650_7 $$2Other$$aoligoadenylates
000279044 650_7 $$2Other$$astructural biology
000279044 650_7 $$2Other$$avirus restriction
000279044 650_7 $$0EC 2.7.7.84$$2NLM Chemicals$$a2',5'-Oligoadenylate Synthetase
000279044 650_7 $$0EC 2.7.7.-$$2NLM Chemicals$$aOAS2 protein, human
000279044 650_7 $$061172-40-5$$2NLM Chemicals$$a2',5'-oligoadenylate
000279044 650_7 $$2NLM Chemicals$$aRNA, Double-Stranded
000279044 650_7 $$0EC 3.1.26.-$$2NLM Chemicals$$a2-5A-dependent ribonuclease
000279044 650_7 $$0EC 3.1.-$$2NLM Chemicals$$aEndoribonucleases
000279044 650_7 $$2NLM Chemicals$$aAdenine Nucleotides
000279044 650_7 $$2NLM Chemicals$$aOligoribonucleotides
000279044 650_2 $$2MeSH$$a2',5'-Oligoadenylate Synthetase: genetics
000279044 650_2 $$2MeSH$$a2',5'-Oligoadenylate Synthetase: chemistry
000279044 650_2 $$2MeSH$$a2',5'-Oligoadenylate Synthetase: metabolism
000279044 650_2 $$2MeSH$$aHumans
000279044 650_2 $$2MeSH$$aGolgi Apparatus: enzymology
000279044 650_2 $$2MeSH$$aGolgi Apparatus: virology
000279044 650_2 $$2MeSH$$aProtein Multimerization
000279044 650_2 $$2MeSH$$aHEK293 Cells
000279044 650_2 $$2MeSH$$aVirus Replication
000279044 650_2 $$2MeSH$$aMutation
000279044 650_2 $$2MeSH$$aRNA, Double-Stranded: metabolism
000279044 650_2 $$2MeSH$$aRNA, Double-Stranded: genetics
000279044 650_2 $$2MeSH$$aHeLa Cells
000279044 650_2 $$2MeSH$$aEndoribonucleases: metabolism
000279044 650_2 $$2MeSH$$aEndoribonucleases: genetics
000279044 650_2 $$2MeSH$$aStructure-Activity Relationship
000279044 650_2 $$2MeSH$$aAdenine Nucleotides
000279044 650_2 $$2MeSH$$aOligoribonucleotides
000279044 7001_ $$aBekere, Indra$$b1
000279044 7001_ $$aKretschmer, Stefanie$$b2
000279044 7001_ $$aSchnell, Adrian F$$b3
000279044 7001_ $$aKmiec, Dorota$$b4
000279044 7001_ $$0P:(DE-2719)9003505$$aSivarajan, Rinu$$b5$$udzne
000279044 7001_ $$aLammens, Katja$$b6
000279044 7001_ $$aLiu, Rou$$b7
000279044 7001_ $$aMergner, Julia$$b8
000279044 7001_ $$aTeppert, Julia$$b9
000279044 7001_ $$0P:(DE-2719)9003503$$aHirschenberger, Maximilian$$b10$$udzne
000279044 7001_ $$aHenrici, Alexander$$b11
000279044 7001_ $$aHammes, Sarah$$b12
000279044 7001_ $$aBuder, Kathrin$$b13
000279044 7001_ $$aWeitz, Marcus$$b14
000279044 7001_ $$aHackmann, Karl$$b15
000279044 7001_ $$aKoenig, Lars M$$b16
000279044 7001_ $$aPichlmair, Andreas$$b17
000279044 7001_ $$aSchwierz, Nadine$$b18
000279044 7001_ $$0P:(DE-2719)9003481$$aSparrer, Konstantin M J$$b19$$udzne
000279044 7001_ $$aLee-Kirsch, Min Ae$$b20
000279044 7001_ $$ade Oliveira Mann, Carina C$$b21
000279044 773__ $$0PERI:(DE-600)2001948-8$$a10.1016/j.molcel.2025.05.001$$gVol. 85, no. 11, p. 2176 - 2193.e13$$n11$$p2176 - 2193.e13$$tMolecular cell$$v85$$x1097-2765$$y2025
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