ArticleNucleic acids research2023
Activation of Csm6 ribonuclease by cyclic nucleotide binding: in an emergency, twist to open.
Article in Nucleic acids research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 23 citations in OpenAlex.
- The CRISPR ring nuclease Csx15 oligomerises on cyclic nucleotide binding to regulate antiviral defence.The Biochemical journal · 2026Article
- Mechanistic basis for selective Csm6-2 activation by cyclic penta-adenylate in a type III CRISPR-Cas system.The EMBO journal · 2026Article
- Structural and functional insights into the adenosine deaminase of the type III-B CRISPR-Cas system.Nucleic acids research · 2026Article
- Structural plasticity enables broad cAn binding and dual activation of CRISPR-associated ribonuclease Cdn1.Nucleic acids research · 2026Article
- Structure and mechanism of the broad spectrum CRISPR-associated ring nuclease Crn4.Nature communications · 2025Article
- Diversity and abundance of ring nucleases in type III CRISPR-Cas loci.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2025Article
- CARF-dependent preferential RNA cleavage by Csm6 increases drug susceptibility of mycobacteria.Nucleic acids research · 2025Article
- Structural integrity and side-chain interaction at the loop region of the bridge helix modulate Cas9 substrate discrimination.Nucleic acids research · 2025Article
- Mechanistic determinants and dynamics of cA6 synthesis in type III CRISPR-Cas effector complexes.Nucleic acids research · 2025Article
- Pulsed EPR Methods in the Angstrom to Nanometre Scale Shed Light on the Conformational Flexibility of a Fluoride Riboswitch.Angewandte Chemie (International ed. in English) · 2024Article
- Selective degradation of phage RNAs by the Csm6 ribonuclease provides robust type III CRISPR immunity in Streptococcus thermophilus.Nucleic acids research · 2024Article
- Structural insight into the Csx1-Crn2 fusion self-limiting ribonuclease of type III CRISPR system.Nucleic acids research · 2024Article
- CRISPR antiphage defence mediated by the cyclic nucleotide-binding membrane protein Csx23.Nucleic acids research · 2024Article
- Molecular mechanism of allosteric activation of the CRISPR ribonuclease Csm6 by cyclic tetra-adenylate.The EMBO journal · 2024Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Type III CRISPR systems synthesize cyclic oligoadenylate (cOA) second messengers as part of a multi-faceted immune response against invading mobile genetic elements (MGEs). cOA activates non-specific CRISPR ancillary defence nucleases to create a hostile environment for MGE replication. Csm6 ribonucleases bind cOA using a CARF (CRISPR-associated Rossmann Fold) domain, resulting in activation of a fused HEPN (Higher Eukaryotes and Prokaryotes Nucleotide binding) ribonuclease domain. Csm6 enzymes are widely used in a new generation of diagnostic assays for the detection of specific nucleic acid species. However, the activation mechanism is not fully understood. Here we characterised the cyclic hexa-adenylate (cA6) activated Csm6' ribonuclease from the industrially important bacterium Streptococcus thermophilus. Crystal structures of Csm6' in the inactive and cA6 bound active states illuminate the conformational changes which trigger mRNA destruction. Upon binding of cA6, there is a close to 60° rotation between the CARF and HEPN domains, which causes the 'jaws' of the HEPN domain to open and reposition active site residues. Key to this transition is the 6H domain, a right-handed solenoid domain connecting the CARF and HEPN domains, which transmits the conformational changes for activation.
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