{"abstract":[{"text":"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.","lang":"eng"}],"external_id":{"pmid":["35624106"]},"publication_status":"published","date_created":"2024-03-20T10:41:59Z","article_processing_charge":"Yes","intvolume":"        13","title":"Structural basis for broad anti-phage immunity by DISARM","article_type":"original","oa_version":"Published Version","date_updated":"2024-06-04T06:16:38Z","quality_controlled":"1","author":[{"orcid":"0000-0003-0456-0753","full_name":"Bravo, Jack Peter Kelly","first_name":"Jack Peter Kelly","last_name":"Bravo","id":"96aecfa5-8931-11ee-af30-aa6a5d6eee0e"},{"first_name":"Cristian","full_name":"Aparicio-Maldonado, Cristian","last_name":"Aparicio-Maldonado"},{"first_name":"Franklin L.","full_name":"Nobrega, Franklin L.","last_name":"Nobrega"},{"first_name":"Stan J. J.","full_name":"Brouns, Stan J. J.","last_name":"Brouns"},{"first_name":"David W.","full_name":"Taylor, David W.","last_name":"Taylor"}],"citation":{"ista":"Bravo JPK, Aparicio-Maldonado C, Nobrega FL, Brouns SJJ, Taylor DW. 2022. Structural basis for broad anti-phage immunity by DISARM. Nature Communications. 13, 2987.","chicago":"Bravo, Jack Peter Kelly, Cristian Aparicio-Maldonado, Franklin L. Nobrega, Stan J. J. Brouns, and David W. Taylor. “Structural Basis for Broad Anti-Phage Immunity by DISARM.” <i>Nature Communications</i>. Springer Nature, 2022. <a href=\"https://doi.org/10.1038/s41467-022-30673-1\">https://doi.org/10.1038/s41467-022-30673-1</a>.","short":"J.P.K. Bravo, C. Aparicio-Maldonado, F.L. Nobrega, S.J.J. Brouns, D.W. Taylor, Nature Communications 13 (2022).","ieee":"J. P. K. Bravo, C. Aparicio-Maldonado, F. L. Nobrega, S. J. J. Brouns, and D. W. Taylor, “Structural basis for broad anti-phage immunity by DISARM,” <i>Nature Communications</i>, vol. 13. Springer Nature, 2022.","mla":"Bravo, Jack Peter Kelly, et al. “Structural Basis for Broad Anti-Phage Immunity by DISARM.” <i>Nature Communications</i>, vol. 13, 2987, Springer Nature, 2022, doi:<a href=\"https://doi.org/10.1038/s41467-022-30673-1\">10.1038/s41467-022-30673-1</a>.","apa":"Bravo, J. P. K., Aparicio-Maldonado, C., Nobrega, F. L., Brouns, S. J. J., &#38; Taylor, D. W. (2022). Structural basis for broad anti-phage immunity by DISARM. <i>Nature Communications</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41467-022-30673-1\">https://doi.org/10.1038/s41467-022-30673-1</a>","ama":"Bravo JPK, Aparicio-Maldonado C, Nobrega FL, Brouns SJJ, Taylor DW. Structural basis for broad anti-phage immunity by DISARM. <i>Nature Communications</i>. 2022;13. doi:<a href=\"https://doi.org/10.1038/s41467-022-30673-1\">10.1038/s41467-022-30673-1</a>"},"article_number":"2987","publisher":"Springer Nature","main_file_link":[{"url":"https://doi.org/10.1038/s41467-022-30673-1","open_access":"1"}],"date_published":"2022-05-27T00:00:00Z","_id":"15133","oa":1,"publication":"Nature Communications","volume":13,"status":"public","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","pmid":1,"type":"journal_article","publication_identifier":{"issn":["2041-1723"]},"month":"05","doi":"10.1038/s41467-022-30673-1","keyword":["General Physics and Astronomy","General Biochemistry","Genetics and Molecular Biology","General Chemistry","Multidisciplinary"],"extern":"1","language":[{"iso":"eng"}],"year":"2022","day":"27","scopus_import":"1"}