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<p>Bacterial CBASS immune defense systems commonly kill virally infected cells by degrading genomic DNA in a form of cell suicide or abortive infection. We present a high-resolution structure of the CBASS effector Cap5, activated by a cyclic nucleotide, in the act of digesting DNA via tetrameric HNH endonuclease domains. Two HNH domains are in a catalytically active state for cleavage of the DNA strands, whereas the other two HNH domains are in a topologically distinct catalytically inactive state for simply DNA binding. The four HNH domains track one face of the DNA and mark an enzyme that acts as a stand-alone non-specific nuclease. We also show that chromosomally encoded CBASS Cap5 can be extrinsically activated by a cyclic nucleotide, as a step towards potential antibiotics.</p>

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Mechanism of DNA degradation by CBASS Cap5 endonuclease immune effector

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年6月5日

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  • Olga Rechkoblit,
  • Daniela Sciaky,
  • Mi Ni,
  • Yangmei Li,
  • Jithesh Kottur,
  • Gang Fang,
  • Aneel K. Aggarwal

摘要

Bacterial CBASS immune defense systems commonly kill virally infected cells by degrading genomic DNA in a form of cell suicide or abortive infection. We present a high-resolution structure of the CBASS effector Cap5, activated by a cyclic nucleotide, in the act of digesting DNA via tetrameric HNH endonuclease domains. Two HNH domains are in a catalytically active state for cleavage of the DNA strands, whereas the other two HNH domains are in a topologically distinct catalytically inactive state for simply DNA binding. The four HNH domains track one face of the DNA and mark an enzyme that acts as a stand-alone non-specific nuclease. We also show that chromosomally encoded CBASS Cap5 can be extrinsically activated by a cyclic nucleotide, as a step towards potential antibiotics.