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CRISPR–Cas systems

CRISPR–Cas has a new juggling act: interplay between nuclease and protease

Nature Structural & Molecular Biology volume 30, pages 126–128 (2023)Cite this article

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Craspase is newly identified type III CRISPR–Cas system with two major components: the nuclease Cas7-11, and the protease TPR-CHAT. Craspases perform a delicate balancing act between nuclease and protease activity to achieve immune tolerance and defense in bacteria, and show promise as highly regulatable genome-editing tools.

The newly identified type III-E system contains a unique structural composition and lacks the canonical Cas10 subunit. Instead, a gene product of four Cas7 domains is naturally fused to a small Csm2/Csm5 subunit (Cas11) to create a single large protein (Cas7-11) capable of self-processing pre-crRNA into mature crRNA and cleaving cognate target RNA at two positions, separated by six nucleotides6 (Fig. 1b). Furthermore, the type III-E system encodes the putative caspase-like protease TPR-CHAT (also known as Csx29) and the three accessory proteins Csx30, Csx31 and RpoE6. Biochemical analysis has shown that Cas7-11 and TPR-CHAT form a biologically active complex named Craspase (CRISPR-guided caspase)6. However, the assembly and activation mechanism of Craspase remained unexplored.

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Fig. 1: Mechanisms of type III CRISPR–Cas systems in prokaryotic immune responses.

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Acknowledgements

T.-M.F. was supported by the National Institutes of Health (NIH) National Institute of General Medical Sciences (grant 1R35GM147465) and A.D.R was supported by an NIH T32 (GM118291-05 and GM144293-01).

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Authors and Affiliations

  1. Department of Biological Chemistry and Pharmacology, The Ohio State University, Columbus, OH, USA

    Anthony D. Rish & Tian-Min Fu

  2. The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA

    Anthony D. Rish & Tian-Min Fu

  3. Program of OSBP, The Ohio State University, Columbus, OH, USA

    Anthony D. Rish & Tian-Min Fu

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  1. Anthony D. Rish
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Correspondence to Tian-Min Fu.

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Rish, A.D., Fu, TM. CRISPR–Cas has a new juggling act: interplay between nuclease and protease. Nat Struct Mol Biol 30, 126–128 (2023). https://doi.org/10.1038/s41594-022-00917-1

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