SNAP output for PDB entry 7s9w [SNAP web server]

PDB-id

7s9w; SNAP-derived features in text and JSON formats; DNAproDB

Class

immune system

Method

cryo-EM (3.4 Å)

Summary

Structure of drmab:adp:DNA complex

Reference

Bravo JPK, Aparicio-Maldonado C, Nobrega FL, Brouns SJJ, Taylor DW (2022): "Structural basis for broad anti-phage immunity by DISARM." Nat Commun, 13, 2987. doi: 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.