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Two Distant Catalytic Sites Are Responsible for C2c2 RNase Activities

  • [设施]:上海设施
  • [期刊/会议名称]:cell
  • [摘要]:C2c2, the effector of type VI CRISPR-Cas systems, has two RNase activities—one for cutting its RNA target and the other for processing the CRISPR RNA (crRNA). Here, we report the structures of Lep-totrichia shahii C2c2 in its crRNA-free and crRNA-bound states. While C2c2 has a bilobed structure reminiscent of all other Class 2 effectors, it also ex-hibits different structural characteristics. It contains the REC lobe with a Helical-1 domain and the NUC lobe with two HEPN domains. The two RNase cata-lytic pockets responsible for cleaving pre-crRNA and target RNA are independently located on Heli-cal-1 and HEPN domains, respectively. crRNA bind-ing induces significant conformational changes that are likely to stabilize crRNA binding and facilitate target RNA recognition. These structures provide important insights into the molecular mechanism of dual RNase activities of C2c2 and establish a frame-work for its future engineering as a RNA editing tool.
  • [发表日期]:2017
  • [第一作者]:Liang Liu
  • [第一作者单位]:CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences
  • [通讯作者]:Yanli Wang
  • [通讯作者单位]:CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences
  • [论文类型]:0
  • [期刊分类]:SCI1
  • [学科分类]:
  • [影响因子]:28.71
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