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Structural basis for broad anti-phage immunity by DISARM
Open accessPreprint — published as 10.1038/s41467-022-30673-1
Abstract
In the evolutionary arms race against phage, bacteria have assembled a diverse arsenal of antiviral immune strategies. While the recently discovered DISARM (Defense Island System Associated with Restriction-Modification) systems can provide protection against a wide range of phage, the molecular mechanisms that underpin broad antiviral targeting but avoiding autoimmunity remain enigmatic. Here, we report cryo-EM structures of the core DISARM complex, DrmAB, both alone and in complex with an unmethylated phage DNA mimetic. These structures reveal that DrmAB core complex is autoinhibited by a trigger loop (TL) within DrmA and binding to DNA substrates containing a 5’ overhang dislodges the TL, initiating a long-range structural rearrangement for DrmAB activation. Together with structure-guided in vivo studies, our work provides insights into the mechanism of phage DNA recognition and specific activation of this widespread antiviral defense system.
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Metadata
- Authors
- Bravo, J. P. K., Aparicio-Maldonado, C., Nobrega, F. L., Brouns, S. J. J., & Taylor, D. W.
- Affiliations
- The University of Texas at Austin (US)
- University of Southampton (GB)
- Delft University of Technology (NL)
- Corresponding author
- Brouns, Stan J. J.
- Taylor, David W.
- Venue
- Nature Communications
- Publisher
- openRxiv
- Published
- 2021-12-27
- Volume
- 13
- Issue
- 1
- Pages
- 2987-2987
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC9142583
- OpenAlex
- W4281999294
- Cited by
- 45
- References
- 1
- Citations by year
- 2026: 14 · 2025: 11 · 2024: 11 · 2023: 8 · 2021: 1
- FWCI
- 4.00
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Nature Communications (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- ePrints Soton (University of Southampton) (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Research Repository (Delft University of Technology) (submittedVersion, cc-by)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Funders
- U.S. Department of Health and Human Services (R35GM138348)
- Cancer Prevention and Research Institute of Texas (RR160088, W911NF-19-1-0021)
- European Commission (101003229, HORIZON2020)
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (VI.C.182.027)
- National Institutes of Health (RR160088)
- National Institute of General Medical Sciences (R35GM138348)
- Army Research Office (W911NF‐19‐1‐0021, W911NF-19-1, RR160088, W911NF, W911NF-19)
- Topics
- Life Sciences › Immunology and Microbiology › Virology › Bacteriophages and microbial interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Keywords
- restriction-modification systems, phage immunity, trigger loop, autoinhibition, structural rearrangement, anti-phage defense, cryo-EM structure
- MeSH terms
- Antiviral Agents, Bacteria, Bacteriophages, Biological Evolution, DNA Restriction-Modification Enzymes
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