8FNU

Structure of RdrA from Streptococcus suis RADAR defense system

Summary for 8FNU

• Entry DOI: 10.2210/pdb8fnu/pdb
• EMDB information: 29326
• Descriptor: KAP NTPase domain-containing protein (1 entity in total)
• Functional Keywords: radar, atpase, rdra, antiphage system, immune system
• Biological source: Streptococcus suis
• Total number of polymer chains: 7
• Total formula weight: 744893.14

Authors

Duncan-Lowey, B.,Johnson, A.G.,Rawson, S.,Mayer, M.L.,Kranzusch, P.J. (deposition date: 2022-12-28, release date: 2023-02-01, Last modification date: 2024-06-19)

Primary citation

Duncan-Lowey, B.,Tal, N.,Johnson, A.G.,Rawson, S.,Mayer, M.L.,Doron, S.,Millman, A.,Melamed, S.,Fedorenko, T.,Kacen, A.,Brandis, A.,Mehlman, T.,Amitai, G.,Sorek, R.,Kranzusch, P.J.
Cryo-EM structure of the RADAR supramolecular anti-phage defense complex.
Cell, 186:987-, 2023

PubMed Abstract: 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.

PubMed: 36764290
DOI: 10.1016/j.cell.2023.01.012

Experimental method

ELECTRON MICROSCOPY (2.5 Å)