PubReading [135] - Structural basis for broad anti-phage immunity by DISARM - J. Bravo, D. Taylor et al

<p>In the evolutionary arms race against <strong>phage</strong>, bacteria have assembled a diverse arsenal of antiviral immune strategies. While the recently discovered <strong>DISARM</strong> (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 <strong>cryo-EM structures</strong> 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 <strong>trigger loop</strong> (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.</p><p>doi.org/10.1038/s41467-022-30673-1 - 2022</p>