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001     279044
005     20250713001351.0
024 7 _ |a 10.1016/j.molcel.2025.05.001
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037 _ _ |a DZNE-2025-00674
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Merold, Veronika
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245 _ _ |a Structural basis for OAS2 regulation and its antiviral function.
260 _ _ |a [Cambridge, Mass.]
|c 2025
|b Cell Press
336 7 _ |a article
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520 _ _ |a Oligoadenylate 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.
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650 _ 7 |a OAS2
|2 Other
650 _ 7 |a RNA sensing
|2 Other
650 _ 7 |a RNase L
|2 Other
650 _ 7 |a innate immunity
|2 Other
650 _ 7 |a localization
|2 Other
650 _ 7 |a oligoadenylates
|2 Other
650 _ 7 |a structural biology
|2 Other
650 _ 7 |a virus restriction
|2 Other
650 _ 7 |a 2',5'-Oligoadenylate Synthetase
|0 EC 2.7.7.84
|2 NLM Chemicals
650 _ 7 |a OAS2 protein, human
|0 EC 2.7.7.-
|2 NLM Chemicals
650 _ 7 |a 2',5'-oligoadenylate
|0 61172-40-5
|2 NLM Chemicals
650 _ 7 |a RNA, Double-Stranded
|2 NLM Chemicals
650 _ 7 |a 2-5A-dependent ribonuclease
|0 EC 3.1.26.-
|2 NLM Chemicals
650 _ 7 |a Endoribonucleases
|0 EC 3.1.-
|2 NLM Chemicals
650 _ 7 |a Adenine Nucleotides
|2 NLM Chemicals
650 _ 7 |a Oligoribonucleotides
|2 NLM Chemicals
650 _ 2 |a 2',5'-Oligoadenylate Synthetase: genetics
|2 MeSH
650 _ 2 |a 2',5'-Oligoadenylate Synthetase: chemistry
|2 MeSH
650 _ 2 |a 2',5'-Oligoadenylate Synthetase: metabolism
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Golgi Apparatus: enzymology
|2 MeSH
650 _ 2 |a Golgi Apparatus: virology
|2 MeSH
650 _ 2 |a Protein Multimerization
|2 MeSH
650 _ 2 |a HEK293 Cells
|2 MeSH
650 _ 2 |a Virus Replication
|2 MeSH
650 _ 2 |a Mutation
|2 MeSH
650 _ 2 |a RNA, Double-Stranded: metabolism
|2 MeSH
650 _ 2 |a RNA, Double-Stranded: genetics
|2 MeSH
650 _ 2 |a HeLa Cells
|2 MeSH
650 _ 2 |a Endoribonucleases: metabolism
|2 MeSH
650 _ 2 |a Endoribonucleases: genetics
|2 MeSH
650 _ 2 |a Structure-Activity Relationship
|2 MeSH
650 _ 2 |a Adenine Nucleotides
|2 MeSH
650 _ 2 |a Oligoribonucleotides
|2 MeSH
700 1 _ |a Bekere, Indra
|b 1
700 1 _ |a Kretschmer, Stefanie
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700 1 _ |a Schnell, Adrian F
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700 1 _ |a Kmiec, Dorota
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700 1 _ |a Sivarajan, Rinu
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700 1 _ |a Lammens, Katja
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700 1 _ |a Liu, Rou
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700 1 _ |a Mergner, Julia
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700 1 _ |a Teppert, Julia
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700 1 _ |a Hirschenberger, Maximilian
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700 1 _ |a Henrici, Alexander
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700 1 _ |a Hammes, Sarah
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700 1 _ |a Buder, Kathrin
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700 1 _ |a Weitz, Marcus
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700 1 _ |a Hackmann, Karl
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700 1 _ |a Koenig, Lars M
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700 1 _ |a Pichlmair, Andreas
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700 1 _ |a Schwierz, Nadine
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700 1 _ |a Sparrer, Konstantin M J
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700 1 _ |a Lee-Kirsch, Min Ae
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700 1 _ |a de Oliveira Mann, Carina C
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773 _ _ |a 10.1016/j.molcel.2025.05.001
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