PT  - JOURNAL ARTICLE
AU  - Bravo, Jack P. K.
AU  - Aparicio-Maldonado, Cristian
AU  - Nobrega, Franklin L.
AU  - Brouns, Stan J. J.
AU  - Taylor, David W.
TI  - Structural basis for broad anti-phage immunity by DISARM
AID  - 10.1101/2021.12.26.474123
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.12.26.474123
4099  - http://biorxiv.org/content/early/2021/12/27/2021.12.26.474123.short
4100  - http://biorxiv.org/content/early/2021/12/27/2021.12.26.474123.full
AB  - 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.Competing Interest StatementThe authors have declared no competing interest.