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Structure paper

TitleCryo-EM structure of the RADAR supramolecular anti-phage defense complex.
Journal, issue, pagesCell, Vol. 186, Issue 5, Page 987-998.e15, Year 2023
Publish dateMar 2, 2023
AuthorsBrianna 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 AbstractRADAR 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.
External linksCell / PubMed:36764290 / PubMed Central
MethodsEM (single particle)
Resolution2.11 - 6.73 Å
Structure data

29323

8fnt

EMDB-29323, PDB-8fnt:
Structure of RdrA from Escherichia coli RADAR defense system
Method: EM (single particle) / Resolution: 2.52 Å

EMDB-29324: Map of RdrA from Escherichia coli RADAR defense system in single-split conformation
Method: EM (single particle) / Resolution: 2.51 Å

EMDB-29325: Map of RdrA from Escherichia coli RADAR defense system in double-split conformation
Method: EM (single particle) / Resolution: 2.35 Å

29326

8fnu

EMDB-29326, PDB-8fnu:
Structure of RdrA from Streptococcus suis RADAR defense system
Method: EM (single particle) / Resolution: 2.5 Å

29327

8fnv

EMDB-29327, PDB-8fnv:
Structure of RdrB from Escherichia coli RADAR defense system
Method: EM (single particle) / Resolution: 2.11 Å

29328

8fnw

EMDB-29328, PDB-8fnw:
Structure of RdrA-RdrB complex from Escherichia coli RADAR defense system
Method: EM (single particle) / Resolution: 6.73 Å

Chemicals

ChemComp-ZN:
Unknown entry

Source
  • escherichia coli (E. coli)
  • streptococcus suis (bacteria)
KeywordsIMMUNE SYSTEM / anti-phage defense / ATPase / RADAR / RdrA / antiphage system / adenosine deaminase

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