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TitleBacterial Shedu immune nucleases share a common enzymatic core regulated by diverse sensor domains.
Journal, issue, pagesMol Cell, Vol. 85, Issue 3, Page 523-536.e6, Year 2025
Publish dateFeb 6, 2025
AuthorsYajie Gu / Huan Li / Amar Deep / Eray Enustun / Dapeng Zhang / Kevin D Corbett /
PubMed AbstractProkaryotes possess diverse anti-bacteriophage immune systems, including the single-protein Shedu nuclease. Here, we reveal the structural basis for activation of Bacillus cereus Shedu. Two ...Prokaryotes possess diverse anti-bacteriophage immune systems, including the single-protein Shedu nuclease. Here, we reveal the structural basis for activation of Bacillus cereus Shedu. Two cryoelectron microscopy structures of Shedu show that it switches between inactive and active states through conformational changes affecting active-site architecture, which are controlled by the protein's N-terminal domain (NTD). We find that B. cereus Shedu cleaves near DNA ends with a 3' single-stranded overhang, likely enabling it to specifically degrade the DNA injected by certain bacteriophages. Bioinformatic analysis of Shedu homologs reveals a conserved nuclease domain with remarkably diverse N-terminal regulatory domains: we identify 79 distinct NTD types falling into eight broad classes, including those with predicted nucleic acid binding, enzymatic, and other activities. Together, these data reveal Shedu as a broad family of immune nucleases with a common nuclease core regulated by diverse NTDs that likely respond to a range of signals.
External linksMol Cell / PubMed:39742666 / PubMed Central
MethodsEM (single particle)
Resolution2.77 - 3.19 Å
Structure data

41281

8ti8

EMDB-41281, PDB-8ti8:
CryoEM structure of Shedu from Bacillus cereus
Method: EM (single particle) / Resolution: 2.9 Å

41282

8ti9

8tia

EMDB-41282, PDB-8ti9:
CryoEM structure of octamer assembly of Shedu nuclease domain from Bacillus cereus
PDB-8tia: CryoEM structure of locally-refined tetramer of Shedu nuclease domain from Bacillus cereus
Method: EM (single particle) / Resolution: 3.19 Å

Source
  • bacillus cereus b4264 (bacteria)
KeywordsDNA BINDING PROTEIN / Shedu / DUF4263 / Bacterial defense systems / Nuclease / Anti-plasmid defense system / PD-(D/E)XK nuclease / Whirly domain / Two-component signaling

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