The CRISPR-associated adenosine deaminase Cad1 converts ATP to ITP to provide antiviral immunity Journal Article
| Authors: | Baca, C. F.; Majumder, P.; Hickling, J. H.; Ye, L.; Teplova, M.; Brady, S. F.; Patel, D. J.; Marraffini, L. A. |
| Article Title: | The CRISPR-associated adenosine deaminase Cad1 converts ATP to ITP to provide antiviral immunity |
| Abstract: | Type III CRISPR systems provide immunity against genetic invaders through the production of cyclic oligo-adenylate (cAn) molecules that activate effector proteins that contain CRISPR-associated Rossman fold (CARF) domains. Here, we characterized the function and structure of an effector in which the CARF domain is fused to an adenosine deaminase domain, CRISPR-associated adenosine deaminase 1 (Cad1). We show that upon binding of cA4 or cA6 to its CARF domain, Cad1 converts ATP to ITP, both in vivo and in vitro. Cryoelectron microscopy (cryo-EM) structural studies on full-length Cad1 reveal an hexameric assembly composed of a trimer of dimers, with bound ATP at inter-domain sites required for activity and ATP/ITP within deaminase active sites. Upon synthesis of cAn during phage infection, Cad1 activation leads to a growth arrest of the host that prevents viral propagation. Our findings reveal that CRISPR-Cas systems employ a wide range of molecular mechanisms beyond nucleic acid degradation to provide adaptive immunity in prokaryotes. © 2024 The Author(s) |
| Keywords: | genetics; nonhuman; protein domain; quality control; metabolism; cytotoxicity; deamination; amino acid sequence; protein purification; escherichia coli; fluorescence microscopy; models, molecular; idiopathic thrombocytopenic purpura; high performance liquid chromatography; adenosine triphosphate; staphylococcus aureus; optical density; molecular model; rna extraction; growth disorder; x-ray crystallography; protein domains; bacterial growth; x ray diffraction; colony forming unit; cryoelectron microscopy; landscape; virus dna; prokaryote; phylogenetic tree; adenine nucleotides; adenine nucleotide; isothermal titration calorimetry; liquid chromatography-mass spectrometry; cryo-em; bacteriophage; adenosine deaminase; staphylococcus; chromatography; staphylococcus epidermidis; article; rna sequencing; crispr; crispr associated protein; crispr cas system; crispr-cas systems; root mean squared error; plaque forming unit; abortive infection; anti-phage defense; carf; cyclic oligoadenylate; desulfomicrobiaceae |
| Journal Title: | Cell |
| Volume: | 187 |
| Issue: | 25 |
| ISSN: | 0092-8674 |
| Publisher: | Cell Press |
| Date Published: | 2024-12-12 |
| Start Page: | 7183 |
| End Page: | 7195.e24 |
| Language: | English |
| DOI: | 10.1016/j.cell.2024.10.002 |
| PUBMED: | 39471810 |
| PROVIDER: | scopus |
| PMCID: | PMC11645235 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledge in the PDF -- Corresponding authors is MSK authors: Dinshaw J. Patel -- Source: Scopus |
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