Nature (London), 2023-02, Vol.614 (7946), p.168-174
2023
Details
- Autor(en) / Beteiligte
- Titel
- Antiviral signalling by a cyclic nucleotide activated CRISPR protease
- Ist Teil von
- Nature (London), 2023-02, Vol.614 (7946), p.168-174
- Ort / Verlag
- England: Nature Publishing Group
- Erscheinungsjahr
- 2023
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- CRISPR defence systems such as the well-known DNA-targeting Cas9 and the RNA-targeting type III systems are widespread in prokaryotes . The latter orchestrates a complex antiviral response that is initiated through the synthesis of cyclic oligoadenylates after recognition of foreign RNA . Among the large set of proteins that are linked to type III systems and predicted to bind cyclic oligoadenylates , a CRISPR-associated Lon protease (CalpL) stood out to us. CalpL contains a sensor domain of the SAVED family fused to a Lon protease effector domain. However, the mode of action of this effector is unknown. Here we report the structure and function of CalpL and show that this soluble protein forms a stable tripartite complex with two other proteins, CalpT and CalpS, that are encoded on the same operon. After activation by cyclic tetra-adenylate (cA ), CalpL oligomerizes and specifically cleaves the MazF homologue CalpT, which releases the extracytoplasmic function σ factor CalpS from the complex. Our data provide a direct connection between CRISPR-based detection of foreign nucleic acids and transcriptional regulation. Furthermore, the presence of a SAVED domain that binds cyclic tetra-adenylate in a CRISPR effector reveals a link to the cyclic-oligonucleotide-based antiphage signalling system.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0028-0836eISSN: 1476-4687DOI: 10.1038/s41586-022-05571-7Titel-ID: cdi_proquest_miscellaneous_2740514013
- Format
- –
- Schlagworte
- Amino acids, Antiviral drugs, Bacteria - enzymology, Bacteria - immunology, Bacteria - metabolism, Bacteria - virology, Bacteriophages - immunology, Bacteriophages - metabolism, CRISPR, CRISPR-Associated Proteins - metabolism, CRISPR-Cas Systems - genetics, CRISPR-Cas Systems - physiology, Cyclic AMP - analogs & derivatives, Cyclic AMP - chemistry, Deoxyribonucleic acid, DNA, Enzyme Activation, Gene Expression Regulation, Bacterial, Gene regulation, Genes, Ligands, Lon protein, Mode of action, Nucleic acids, Nucleotides, Nucleotides, Cyclic - immunology, Nucleotides, Cyclic - metabolism, Oligomerization, Oligonucleotides, Operon, Protease, Protease La - chemistry, Protease La - metabolism, Proteinase, Proteins, RNA, Viral, Sigma Factor, Signalling systems, Structure-function relationships, Transcription, Genetic