Structural basis for broad anti-phage immunity by DISARM

Bravo JPK, Aparicio-Maldonado C, Nobrega FL, Brouns SJJ, Taylor DW. 2022. Structural basis for broad anti-phage immunity by DISARM. Nature Communications. 13, 2987.

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Bravo, JackISTA ; Aparicio-Maldonado, Cristian; Nobrega, Franklin L.; Brouns, Stan J. J.; Taylor, David W.
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.
Publishing Year
Date Published
2022-05-27
Journal Title
Nature Communications
Volume
13
Article Number
2987
ISSN
IST-REx-ID

Cite this

Bravo JPK, Aparicio-Maldonado C, Nobrega FL, Brouns SJJ, Taylor DW. Structural basis for broad anti-phage immunity by DISARM. Nature Communications. 2022;13. doi:10.1038/s41467-022-30673-1
Bravo, J. P. K., Aparicio-Maldonado, C., Nobrega, F. L., Brouns, S. J. J., & Taylor, D. W. (2022). Structural basis for broad anti-phage immunity by DISARM. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-022-30673-1
Bravo, Jack Peter Kelly, Cristian Aparicio-Maldonado, Franklin L. Nobrega, Stan J. J. Brouns, and David W. Taylor. “Structural Basis for Broad Anti-Phage Immunity by DISARM.” Nature Communications. Springer Nature, 2022. https://doi.org/10.1038/s41467-022-30673-1.
J. P. K. Bravo, C. Aparicio-Maldonado, F. L. Nobrega, S. J. J. Brouns, and D. W. Taylor, “Structural basis for broad anti-phage immunity by DISARM,” Nature Communications, vol. 13. Springer Nature, 2022.
Bravo JPK, Aparicio-Maldonado C, Nobrega FL, Brouns SJJ, Taylor DW. 2022. Structural basis for broad anti-phage immunity by DISARM. Nature Communications. 13, 2987.
Bravo, Jack Peter Kelly, et al. “Structural Basis for Broad Anti-Phage Immunity by DISARM.” Nature Communications, vol. 13, 2987, Springer Nature, 2022, doi:10.1038/s41467-022-30673-1.
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