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<p>Upon sensing nonself target RNA, the CorA-associated type III-B CRISPR–Cas system catalyzes <i>S</i>-adenosyl methionine (SAM) and ATP to synthesize SAM-AMP, which activates the effector CorA and triggers immune responses. SAM-AMP can be degraded by NrN and SAM lyase, potentially deactivating the system. Here we find that the type III-B effector complex from <i>Bacteroides</i> <i>fragilis</i> uses a specific mechanism to recognize nonself target RNA and synthesize SAM-AMP. The 3′ anti-tag of nonself target RNA induces conformational changes in the Cmr2 subunit, triggering SAM-AMP synthesis independently of the stalk loop of Cmr3 subunit. SAM-AMP binding induces NrN to transit from an open to a closed conformation, enabling hydrolysis of the 3′–5′ phosphodiester bond. SAM lyase forms a triangular trimer that specifically degrades SAM-AMP into 5′-methylthioadenosine-AMP and homoserine lactone. These findings unveil unique mechanisms for SAM-AMP synthesis and degradation and provide deeper insights into the molecular basis of type III CRISPR–Cas signaling.</p><p></p>

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Molecular basis of SAM-AMP synthesis and degradation in the type III-B CRISPR–Cas system

  • 期刊论文

  • 发表日期：

    2025年11月21日

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  • Benzhen Duan,
  • Xiaohui Jin,
  • Xiaoman An,
  • Yang Xiao,
  • Qianxi Yang,
  • Hongyu Zhao,
  • Yunxiao Huang,
  • Jingwen Wang,
  • Qian Wang,
  • Fenglei Du,
  • Lu Lu,
  • Lei Sun,
  • Zhenguo Chen,
  • Baoyu Zhao

摘要

Upon sensing nonself target RNA, the CorA-associated type III-B CRISPR–Cas system catalyzes S-adenosyl methionine (SAM) and ATP to synthesize SAM-AMP, which activates the effector CorA and triggers immune responses. SAM-AMP can be degraded by NrN and SAM lyase, potentially deactivating the system. Here we find that the type III-B effector complex from Bacteroides fragilis uses a specific mechanism to recognize nonself target RNA and synthesize SAM-AMP. The 3′ anti-tag of nonself target RNA induces conformational changes in the Cmr2 subunit, triggering SAM-AMP synthesis independently of the stalk loop of Cmr3 subunit. SAM-AMP binding induces NrN to transit from an open to a closed conformation, enabling hydrolysis of the 3′–5′ phosphodiester bond. SAM lyase forms a triangular trimer that specifically degrades SAM-AMP into 5′-methylthioadenosine-AMP and homoserine lactone. These findings unveil unique mechanisms for SAM-AMP synthesis and degradation and provide deeper insights into the molecular basis of type III CRISPR–Cas signaling.