Structural basis for broad anti-phage immunity by DISARM

Structural basis for broad anti-phage immunity by DISARM

Bravo, Jack P.K. (The University of Texas at Austin)
Aparicio Maldonado, C. (TU Delft BN/Stan Brouns Lab; Kavli institute of nanoscience Delft; University of Southampton)
Nobrega, Franklin L. (University of Southampton)
Brouns, S.J.J. (TU Delft BN/Stan Brouns Lab; Kavli institute of nanoscience Delft)
Taylor, David W. (The University of Texas at Austin; Dell Medical School, Austin)

2022

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.

http://resolver.tudelft.nl/uuid:26a616c8-2039-48f5-aa8e-84725972db38

https://doi.org/10.1038/s41467-022-30673-1

2041-1723

Nature Communications, 13 (1)

Institutional Repository

journal article

© 2022 Jack P.K. Bravo, C. Aparicio Maldonado, Franklin L. Nobrega, S.J.J. Brouns, David W. Taylor