Structure and mechanism of a Type III CRISPR defence DNA nuclease activated by cyclic oligoadenylate
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Date
24/01/2020Grant ID
BB/S000313/1
BB/R008035/1
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Abstract
The CRISPR system provides adaptive immunity against mobile genetic elements in prokaryotes. On binding invading RNA species, Type III CRISPR systems generate cyclic oligoadenylate (cOA) signalling molecules, potentiating a powerful immune response by activating downstream effector proteins, leading to viral clearance, cell dormancy or death. Here we describe the structure and mechanism of a cOA-activated CRISPR defence DNA endonuclease, CRISPR ancillary nuclease 1 (Can1). Can1 has a unique monomeric structure with two CRISPR associated Rossman fold (CARF) domains and two DNA nuclease-like domains. The crystal structure of the enzyme has been captured in the activated state, with a cyclic tetra-adenylate (cA4) molecule bound at the core of the protein. cA4 binding reorganises the structure to license a metal-dependent DNA nuclease activity specific for nicking of supercoiled DNA. DNA nicking by Can1 is predicted to slow down viral replication kinetics by leading to the collapse of DNA replication forks.
Citation
McMahon , S , Zhu , W , Graham , S , Rambo , R , White , M & Gloster , T 2020 , ' Structure and mechanism of a Type III CRISPR defence DNA nuclease activated by cyclic oligoadenylate ' , Nature Communications , vol. 11 , 500 . https://doi.org/10.1038/s41467-019-14222-x
Publication
Nature Communications
Status
Peer reviewed
ISSN
2041-1723Type
Journal article
Rights
Copyright © The Author(s) 2020. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Description
Funding: UK Biotechnology and Biological Sciences Research Council (REF: BB/S000313/1 to MFW and REF: BB/R008035/1 to TMG); the China Scholarship Council (REF: 201703780015 to WZ).Collections
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