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Cpf1 shape-shifts for streamlined CRISPR cleavage

Nature Structural & Molecular Biology volume 23, pages 365–366 (2016)Cite this article

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Two new studies of the CRISPR nuclease Cpf1 reveal the structural and catalytic flexibility of this leaner, meaner alternative to Cas9.

Two publications on the programmable CRISPR endonuclease Cpf1, a distant cousin of Cas9, reveal new details about its structure and mechanism. First, Dong et al.1 report the crystal structure of Cpf1 bound to CRISPR RNA (crRNA), revealing important new insights into its molecular architecture. Accompanying biophysical and EM studies reveal that Cpf1 undergoes a substantial conformational change from an extended to a compact structure upon binding crRNA1. A second report by Fonfara et al.2 focuses on the crRNA-processing activity of Cpf1 and demonstrates that the enzyme is responsible for the cleavage of pre-crRNA, thus yielding the mature form used for homology-directed cleavage of DNA targets. The catalytic residues identified by Fonfara et al.2 cluster in the Cpf1 structure at positions adjacent to the 5′ end of the crRNA, thus providing a fine example of the synergistic power of biochemical and structural analyses.

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Figure 1: Structure and domain organization of the Cpf1 protein.
Figure 2: Conformational change of Cpf1 after crRNA binding.

References

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Acknowledgements

Thanks to C. Rollie for helpful discussions. M.F.W. is supported as a Royal Society Wolfson Research Merit Award holder.

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  1. Malcolm F. White is at the Biomedical Sciences Research Complex, University of St Andrews, St Andrews, UK.,

    Malcolm F White

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Correspondence to Malcolm F White.

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White, M. Cpf1 shape-shifts for streamlined CRISPR cleavage. Nat Struct Mol Biol 23, 365–366 (2016). https://doi.org/10.1038/nsmb.3225

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