Year: 2022
Type: article
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.
Source: Nature Communications
Language: English
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,890
Awards: G1449763142, G2279853913, G2661318238, G3024053924, Uncovering the molecular basis of Cas4-mediated CRISPR memory formation, G434337789, G5610185537, Imaging macromolecular machines in gene regulation, Recruitment of First-Time, Tenure-Track Faculty Members, G7334195024, G7452299184, G8415477955, G8872807966
OpenAlex ID: W4281999294