Structure and mechanism of a Type III CRISPR defence DNA nuclease activated by cyclic oligoadenylate.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 31980625.
- Also identified by DOI 10.1038/s41467-019-14222-x and PMC identifier 6981274.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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 (cA<sub>4</sub>) molecule bound at the core of the protein. cA<sub>4</sub> 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.
Medical subject headings
- Adenine Nucleotides
- Clustered Regularly Interspaced Short Palindromic Repeats
- Endonucleases
- Oligoribonucleotides