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-Structure paper
タイトル | Cryo-EM structure of the RADAR supramolecular anti-phage defense complex. |
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ジャーナル・号・ページ | Cell, Vol. 186, Issue 5, Page 987-998.e15, Year 2023 |
掲載日 | 2023年3月2日 |
著者 | Brianna Duncan-Lowey / Nitzan Tal / Alex G Johnson / Shaun Rawson / Megan L Mayer / Shany Doron / Adi Millman / Sarah Melamed / Taya Fedorenko / Assaf Kacen / Alexander Brandis / Tevie Mehlman / Gil Amitai / Rotem Sorek / Philip J Kranzusch / |
PubMed 要旨 | RADAR is a two-protein bacterial defense system that was reported to defend against phage by "editing" messenger RNA. Here, we determine cryo-EM structures of the RADAR defense complex, revealing ...RADAR is a two-protein bacterial defense system that was reported to defend against phage by "editing" messenger RNA. Here, we determine cryo-EM structures of the RADAR defense complex, revealing RdrA as a heptameric, two-layered AAA+ ATPase and RdrB as a dodecameric, hollow complex with twelve surface-exposed deaminase active sites. RdrA and RdrB join to form a giant assembly up to 10 MDa, with RdrA docked as a funnel over the RdrB active site. Surprisingly, our structures reveal an RdrB active site that targets mononucleotides. We show that RdrB catalyzes ATP-to-ITP conversion in vitro and induces the massive accumulation of inosine mononucleotides during phage infection in vivo, limiting phage replication. Our results define ATP mononucleotide deamination as a determinant of RADAR immunity and reveal supramolecular assembly of a nucleotide-modifying machine as a mechanism of anti-phage defense. |
リンク | Cell / PubMed:36764290 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.11 - 6.73 Å |
構造データ | EMDB-29323, PDB-8fnt: EMDB-29324: Map of RdrA from Escherichia coli RADAR defense system in single-split conformation EMDB-29325: Map of RdrA from Escherichia coli RADAR defense system in double-split conformation EMDB-29326, PDB-8fnu: EMDB-29327, PDB-8fnv: EMDB-29328, PDB-8fnw: |
化合物 | ChemComp-ZN: |
由来 |
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キーワード | IMMUNE SYSTEM / anti-phage defense / ATPase / RADAR / RdrA / antiphage system / adenosine deaminase |