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Structural basis for broad anti-phage immunity by DISARM

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 mec...

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Autores principales: Bravo, Jack P. K., Aparicio-Maldonado, Cristian, Nobrega, Franklin L., Brouns, Stan J. J., Taylor, David W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9142583/
https://www.ncbi.nlm.nih.gov/pubmed/35624106
http://dx.doi.org/10.1038/s41467-022-30673-1
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author Bravo, Jack P. K.
Aparicio-Maldonado, Cristian
Nobrega, Franklin L.
Brouns, Stan J. J.
Taylor, David W.
author_facet Bravo, Jack P. K.
Aparicio-Maldonado, Cristian
Nobrega, Franklin L.
Brouns, Stan J. J.
Taylor, David W.
author_sort Bravo, Jack P. K.
collection PubMed
description 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.
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spelling pubmed-91425832022-05-29 Structural basis for broad anti-phage immunity by DISARM Bravo, Jack P. K. Aparicio-Maldonado, Cristian Nobrega, Franklin L. Brouns, Stan J. J. Taylor, David W. Nat Commun Article 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. Nature Publishing Group UK 2022-05-27 /pmc/articles/PMC9142583/ /pubmed/35624106 http://dx.doi.org/10.1038/s41467-022-30673-1 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Bravo, Jack P. K.
Aparicio-Maldonado, Cristian
Nobrega, Franklin L.
Brouns, Stan J. J.
Taylor, David W.
Structural basis for broad anti-phage immunity by DISARM
title Structural basis for broad anti-phage immunity by DISARM
title_full Structural basis for broad anti-phage immunity by DISARM
title_fullStr Structural basis for broad anti-phage immunity by DISARM
title_full_unstemmed Structural basis for broad anti-phage immunity by DISARM
title_short Structural basis for broad anti-phage immunity by DISARM
title_sort structural basis for broad anti-phage immunity by disarm
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9142583/
https://www.ncbi.nlm.nih.gov/pubmed/35624106
http://dx.doi.org/10.1038/s41467-022-30673-1
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