CRISPR-CAS

A stop to signaling

Nature 577, 572–575 (2020)

Bacteria use CRISPR–Cas as an adaptive immune system against viral infection and exogenous nucleic acids. In particular, type III CRISPR–Cas systems can synthesize cyclic oligoadenylates as secondary messengers which bind and activate nucleases to degrade viral nucleic acids. Accordingly, viruses have evolved anti-CRISPR systems (Acr) as a response. Athukoralage et al. identified the DUF1874 protein family as an Acr ring nuclease that degrades cyclic tetraadenylate (cA4). A virus lacking the duf1874 gene lost its infectious ability in an engineered bacterial strain selectively expressing the type III CRISPR–Cas system, but viral infection could be recovered by deletion of the cA4-activated effector Csx1. Structural characterization of the DUF1874 protein in complex with cA4 revealed that cA4 binds in a central pocket, inducing the movement of a loop and helix that buries cA4 inside. The essential catalytic residue His47 of each monomer is positioned toward the 2′-hydroxyl group in cA4 for nucleophilic attack. These findings add a new family to known Acr systems and reflect the continuing evolution of viral evasion strategies.

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Correspondence to Yiyun Song.

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Song, Y. A stop to signaling. Nat Chem Biol 16, 225 (2020). https://doi.org/10.1038/s41589-020-0488-y

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