Tetramerisation of the CRISPR ring nuclease Crn3/Csx3 facilitates cyclic oligoadenylate cleavage
- University of St Andrews, United Kingdom
Abstract
Type III CRISPR systems detect foreign RNA and activate the cyclase domain of the Cas10 subunit, generating cyclic oligoadenylate (cOA) molecules that act as a second messenger to signal infection, activating nucleases that degrade the nucleic acid of both invader and host. This can lead to dormancy or cell death; to avoid this, cells need a way to remove cOA from the cell once a viral infection has been defeated. Enzymes specialised for this task are known as ring nucleases, but are limited in their distribution. Here, we demonstrate that the widespread CRISPR associated protein Csx3, previously described as an RNA deadenylase, is a ring nuclease that rapidly degrades cyclic tetra-adenylate (cA4). The enzyme has an unusual cooperative reaction mechanism involving an active site that spans the interface between two dimers, sandwiching the cA4 substrate. We propose the name Crn3 (CRISPR associated ring nuclease 3) for the Csx3 family.
Data availability
Diffraction data have been deposited in the PDB under the accession code 6YUD.
Article and author information
Author details
Januka S Athukoralage
Funding
Biotechnology and Biological Sciences Research Council (BB/S000313/1)
- Sabine Grüschow
- Shirley Graham
- Malcolm F White
Biotechnology and Biological Sciences Research Council (BB/T004789/1)
- Stuart McQuarrie
- Sabine Grüschow
- Tracey M Gloster
- Malcolm F White
Wellcome Trust Institutional Strategic Support Fund (204821/Z/16/Z)
- Stuart McQuarrie
- Tracey M Gloster
- Malcolm F White
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2020, Athukoralage et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Tetramerisation of the CRISPR ring nuclease Crn3/Csx3 facilitates cyclic oligoadenylate cleavage
eLife 9:e57627.
https://doi.org/10.7554/eLife.57627
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