Structural basis for broad anti-phage immunity by DISARM
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 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.
Bravo, Jack P.K.
b59c3de9-a7ac-4e03-a6b8-7d8bd4763696
Aparicio-Maldonado, Cristian
336d135a-3e11-4e25-a26f-34965940aee2
Luzia De Nobrega, Franklin
6532795d-88a4-4f05-9b26-6af5b8f21a0d
Brouns, Stan J.J.
b9c93a6a-120b-476b-8394-048e41d8ae79
Taylor, David W.
c22699d2-1147-45ad-84fd-57a1cf0369cc
Bravo, Jack P.K.
b59c3de9-a7ac-4e03-a6b8-7d8bd4763696
Aparicio-Maldonado, Cristian
336d135a-3e11-4e25-a26f-34965940aee2
Luzia De Nobrega, Franklin
6532795d-88a4-4f05-9b26-6af5b8f21a0d
Brouns, Stan J.J.
b9c93a6a-120b-476b-8394-048e41d8ae79
Taylor, David W.
c22699d2-1147-45ad-84fd-57a1cf0369cc
Bravo, Jack P.K., Aparicio-Maldonado, Cristian, Luzia De Nobrega, Franklin, Brouns, Stan J.J. and Taylor, David W.
(2022)
Structural basis for broad anti-phage immunity by DISARM.
Nature Communications, 13, [2987].
(doi:10.1101/2021.12.26.474123).
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.
Text
2021.12.26.474123v1.full
- Author's Original
Restricted to Repository staff only
Request a copy
Text
s41467-022-30673-1
- Version of Record
More information
In preparation date: 26 December 2021
e-pub ahead of print date: 27 May 2022
Identifiers
Local EPrints ID: 456379
URI: http://eprints.soton.ac.uk/id/eprint/456379
ISSN: 2041-1723
PURE UUID: 7e0a0df9-f6e5-4e07-9331-601c4e2d9215
Catalogue record
Date deposited: 27 Apr 2022 15:23
Last modified: 17 Mar 2024 04:02
Export record
Altmetrics
Contributors
Author:
Jack P.K. Bravo
Author:
Cristian Aparicio-Maldonado
Author:
Stan J.J. Brouns
Author:
David W. Taylor
Download statistics
Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.
View more statistics
