2. Academic Validation
  3. Multiple enzymatic activities of a Sir2-HerA system cooperate for anti-phage defense

Multiple enzymatic activities of a Sir2-HerA system cooperate for anti-phage defense

  • Mol Cell. 2023 Dec 21;83(24):4600-4613.e6. doi: 10.1016/j.molcel.2023.11.010.
Dongmei Tang 1,  Yijun Chen 2,  Hao Chen 2,  Tingting Jia 2,  Qiang Chen 3,  Yamei Yu 4
Affiliations

Affiliations

  • 1 Department of Urology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.
  • 2 Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.
  • 3 Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China. Electronic address: qiang_chen@scu.edu.cn.
  • 4 Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China. Electronic address: yamei_yu@scu.edu.cn.
PMID: 38096825 DOI: 10.1016/j.molcel.2023.11.010
Abstract

In response to the persistent exposure to phage Infection, bacteria have evolved diverse Antiviral defense mechanisms. In this study, we report a Bacterial two-component defense system consisting of a Sir2 NADase and a HerA helicase. Cryo-electron microscopy reveals that Sir2 and HerA assemble into a ∼1 MDa supramolecular octadecamer. Unexpectedly, this complex exhibits various enzymatic activities, including ATPase, NADase, helicase, and Nuclease, which work together in a sophisticated manner to fulfill the antiphage function. Therefore, we name this defense system "Nezha" after a divine warrior in Chinese mythology who employs multiple weapons to defeat enemies. Our findings demonstrate that Nezha could sense phage infections, self-activate to arrest cell growth, eliminate phage genomes, and subsequently deactivate to allow for cell recovery. Collectively, Nezha represents a paradigm of sophisticated and multifaceted strategies bacteria use to defend against viral infections.

Keywords

HerA; Sir2; anti-phage; auto-regulation; defense system; supramolecular assembly.

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